[Show abstract][Hide abstract] ABSTRACT: Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is related to increased morbidity and mortality. The aim of the present study was to examine whether LV deformational and torsional parameters can predict LV remodeling in patients with AMI.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: NOS inhibitors are a potential treatment for patients with cardiogenic shock during acute myocardial infarction. Despite hemodynamic efficacy, their effects on the extent of myocardial infarction (MI) and the no-reflow phenomenon (NRP) have not been clarified. METHODS: Sixteen pigs underwent occlusion of the mid left anterior descending coronary artery for 1h followed by reperfusion for 2h. Coronary blood flow (CBF), distal to the occlusion site, was measured. In eight experiments, l-NAME (non selective NO synthetase inhibitor) administration began 10min before the onset of reperfusion and continued for 2h (loading dose 1mg/kg, perfusion rate: 1mg/kg/h) (l-NAME group). Eight pigs received similarly normal saline (controls). At the end of each experiment, the myocardial area at risk (MAR) and extent of MI and NRP were measured. RESULTS: Hemodynamics at baseline and during ischemia were similar in both groups. During reperfusion, the mean aortic blood pressure was significantly higher in the l-NAME group. In both groups, CBF reached a peak at 5min of reperfusion, (no difference between groups). CBF gradually returned to baseline levels within 60min of reperfusion in both groups. No statistically significant differences in the extent of the NRP (51.8±19.7 vs 60.9±11.4 p=0.35) and MI (77.9±13.9 vs 77.1±8.8 p=0.92), both expressed as a percentage of MAR, were observed between the l-NAME group and the control group. CONCLUSIONS: l-NAME administration started immediately before and maintained throughout reperfusion has no effect on NRP and MI size. l-NAME might stabilize patients with post-MI cardiogenic shock without adverse effects on infarct size.
International journal of cardiology 09/2012; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Volume overload is a common manifestation of heart failure decompensation. Interaction between impaired renal and heart function constitutes an important pathophysiologic mechanism that leads to congestion. In addition to improving symptoms and volume status, reduction of rehospitalization rates, maintenance of renal function and improvement of survival are all important goals of every therapeutic strategy. Currently, the use of diuretics, vasodilators, inotropes and ultrafiltration, together with investigational agents such as oral vasopressin antagonists and adenosine A1-receptor antagonists, constitute the main therapeutic options for the congested heart failure patient.
Expert Review of Cardiovascular Therapy 09/2011; 9(9):1181-91.
[Show abstract][Hide abstract] ABSTRACT: The effects of the intra-aortic balloon pump (IABP) counterpulsation on the extent of myocardial infarction (MI), the no-reflow phenomenon (NRP), and coronary blood flow (CBF) during reperfusion in an ischemia-reperfusion experimental model have not been clarified. Eleven pigs underwent occlusion of the mid left anterior descending coronary artery for 1 h, followed by reperfusion for 2 h. CBF, distal to the occlusion site, was measured. In six experiments, IABP support began 10 min before, and continued throughout reperfusion (IABP Group). Five pigs without IABP support served as controls. At the end of each experiment, the myocardial area at risk (MAR) of infarction and the extent of MI and NRP were measured. Hemodynamic measurements at baseline and during coronary occlusion were similar in both groups. During reperfusion, systolic aortic blood pressure was significantly lower in the IABP Group than in controls. In the IABP Group, CBF reached a peak at 5 min of reperfusion, gradually decreased, but remained higher than at baseline, and significantly higher than in controls throughout the 2 h of reperfusion. In controls, CBF increased significantly above baseline immediately after the onset of reperfusion, then returned to baseline within 90 min. The extent of NRP (37 ± 25% vs. 68 ± 17%, P = 0.047) and MI (39 ± 23% vs. 67 ± 13%, P = 0.036), both expressed as percentage of MAR, was significantly less in the IABP group than in controls. After prolonged myocardial ischemia, IABP assistance started just 10 min before and throughout reperfusion increased CBF and limited infarct size and extent of NRP.
[Show abstract][Hide abstract] ABSTRACT: Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI.
Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction.
Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI.
CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 07/2011; 24(7):808-14. · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [(18)F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = -0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival.
Archiv für Kreislaufforschung 06/2011; 106(6):1379-86. · 7.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypoxia-inducible factor-1alpha (HIF-1α) expression promotes angiogenesis and can influence stem cell engraftment. We investigated the effect of stable over-expression of constitutively active HIF-1α on cardiosphere-derived cell (CDC) engraftment and left ventricular function. CDCs were transduced with a lentivirus expressing a constitutively active mutant of human HIF-1α (LVHIF-1α). Two million male rat CDCs were injected into the infarct following ligation of the mid-LAD in female syngeneic rats. Left ventricular ejection fraction (EF) and circumferential strain were measured by echocardiography at 1 and 4 weeks post-MI in the following groups: PBS group (n = 7), CELL group (n = 7), and CELL-HIF group (n = 7). HIF-1α, VEGF, endothelin-1 expression, and CDC engraftment were measured by quantitative PCR. At 30 days, EF was unchanged in the CELL-HIF group (p = NS), increased in the CELL group (p = 0.025), and decreased in the PBS group (p = 0.021), but engraftment was similar (2.4% ± 3.3% vs 1.7% ± 0.8%, p = NS). Mean circumferential strain of the infarcted region was unchanged in the CELL-HIF group, but improved in the CELL group (p = 0.02). Endothelin-1 and VEGF expression were higher in HIF-CDCs exposed to hypoxia, compared with non-transduced CDCs. HIF-1α expression in CDCs blunted the beneficial functional effects of CDC transplantation, suggesting that paracrine factor balance may play an important role in cardiac regeneration.
Journal of Cardiovascular Translational Research 06/2011; 4(3):363-72. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inotrope treatment is often necessary in refractory to optimal management end stage heart failure, when signs of end-organ hypoperfusion appear. The effect of specific inotropes on patient outcome remains controversial. The aim of the study was to compare the effect of levosimendan versus dobutamine, alone or in combination with levosimendan, on the outcome of end-stage heart failure patients, requiring inotropic therapy.
We studied 63 patients in NYHA class IV, refractory to optimal medical therapy, recently hospitalized for cardiac decompensation and stabilized by an intravenous inotrope. They were randomly assigned to intermittent infusions of either a) dobutamine, 10mg/kg/min, versus b) levosimendan, 0.3mg/kg/min, versus c) dobutamine, 10mg/kg/min+levosimendan 0.2 mg/kg/min, each administered weekly, for 6h, over a 6-month period. All patients received amiodarone, 400 mg/day, to suppress the proarrhythmic effects of the inotropes. Baseline characteristics of the 3 groups were similar. At 6 months, survival free from death or urgent left ventricular device implantation was 80% in the levosimendan, 48% in the dobutamine (P=0.037 versus levosimendan), and 43% in the levosimendan+dobutamine (P=0.009 versus levosimendan) group. At 3months, NYHA class improved significantly in all 3 groups, whereas pulmonary capillary wedge pressure decreased (27 ± 4 to 19 ± 8 mmHg, P=0.008) and cardiac index increased (1.5 ± 0.3 to 2.1 ± 0.3 l/min/m(2), P=0.002) significantly only in patients assigned to levosimendan.
In patients with refractory end-stage heart failure, intermittent administration of levosimendan conferred survival and hemodynamic benefits in comparison to a regimen of intermittent infusions of dobutamine, alone or in combination with levosimendan.
International journal of cardiology 04/2011; 159(3):225-9. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment.
We studied acute(1 hour) cardiac/lung retention in 4 groups (n = 25) of rats (normal--NL, acute ischemia-reperfusion--AI-RM, acute permanent ligation-PL, and chronic infarct by ischemia-reperfusion--CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n = 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n = 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs. 12.0% ± 3.9% vs. 9.9 ± 2.8 vs. 15.4% ± 5.5%; P = NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs. AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection.
Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.
Journal of Nuclear Cardiology 03/2011; 18(3):443-50. · 2.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia-reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30 min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2 h of reperfusion predicted a larger IA (r = 0.71; p = 0.001). Time-to-development of retrograde CBF was inversely related to IA (r = -0.55; p = 0.019) and NR (r = -0.62; p = 0.006). A larger IA (OR 1.12, 95% CI 1.01-1.24, p = 0.037) and NR (OR 1.09, 95% CI 1.01-1.18, p = 0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level.
Journal of Cardiovascular Translational Research 02/2011; 4(1):99-105. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET).
Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery.
The CDCs were derived from syngeneic, male Wistar Kyoto (WK) rats labeled with [(18)F]-fluoro-deoxy-glucose ((18)FDG) and injected intramyocardially into the ischemic region of female WK rats after permanent left coronary artery ligation. The effects of fibrin glue (FG), bradycardia (adenosine), and cardiac arrest were examined. Imaging with (18)FDG PET was performed for quantification of cell retention. Quantitative polymerase chain reaction (PCR) for the male-specific SRY gene was performed to validate the PET results.
Myocardial retention of cells suspended in phosphate-buffered saline 1 h after delivery was 17.6 +/- 11.5% by PCR and 17.8 +/- 7.3% by PET. When CDCs were injected immediately after induction of cardiac arrest, retention was increased to 75.6 +/- 18.6%. Adenosine slowed the ventricular rate and doubled CDC retention (35.4 +/- 5.3%). A similar increase in CDC retention was observed after epicardial application of FG at the injection site (37.5 +/- 8.2%). The PCR revealed a significant increase in 3-week cell engraftment in the FG animals (22.1 +/- 18.6% and 5.3 +/- 3.1%, for FG and phosphate-buffered saline, respectively).
In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with FG or lowering ventricular rate by adenosine might be clinically translatable methods for improving stem cell engraftment in a beating heart.
Journal of the American College of Cardiology 10/2009; 54(17):1619-26. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiogenic shock is the leading cause of death during hospitalization for acute myocardial infarction (MI). However, little data exist regarding the long-term outcomes of patients who survived the acute phase of MI and were discharged from the hospital.
We retrospectively reviewed the records of 81 consecutive patients referred for management of acute MI and cardiogenic shock to analyze their in-hospital and long-term outcomes.
Mean systemic systolic and central venous pressures at presentation were 74 +/- 15 and 17 +/- 7 mm Hg, respectively. Intra-aortic balloon counterpulsation (IABC) was implemented in all patients for a mean of 88 +/- 83 hours. Thrombolytics were administered in 49% and mechanical ventilation applied in 46% of patients. Primary angioplasty could not be performed in any patient, while 17 patients later underwent myocardial revascularization during hospitalization. There were 37 in-hospital survivors (45.7%). The 1-year survival after discharge from the hospital was 87.6% in the overall population, versus 100% among patients who underwent in-hospital myocardial revascularization, versus 78.9% among nonrevascularized patients (p = 0.079). Over a mean follow-up of 85 +/- 47 mo, survival after discharge from the index hospitalization was 44.9% in the overall population, versus 56.2% among revascularized patients, versus 36.4% among nonrevascularized patients (p = 0.277). Heart failure developed in 51.6% of patients who were discharged from the hospital.
In this single center analysis, the long-term survival after acute MI complicated by cardiogenic shock was high with nearly 50% of patients surviving free from heart failure.
[Show abstract][Hide abstract] ABSTRACT: Concern has been raised regarding the mortality and ethics related to the treatment of patients with end-stage chronic heart failure with chronic intermittent intravenous inotropic agents. We examined whether intermittent inotropic agents combined with oral amiodarone to prevent the proarrhythmic effect of inotropic agents results in better outcomes.
The study included 162 patients with decompensated end-stage chronic heart failure, who could be weaned from an initial 72-hour infusion of intravenous inotropes. Group 1 included 140 patients, who entered a 6-month program of weekly intermittent intravenous inotropic agents plus oral amiodarone, 200 mg twice a day. Group 2 included 22 patients, who were treated with optimal conventional therapy and were hospitalized for administration of intravenous medications as needed.
The baseline characteristics of groups 1 versus 2, including New York Heart Association functional class (IV in both groups), admission systolic arterial blood pressure (99 +/- 14 vs. 97 +/- 13 mm Hg), right atrial pressure (13 +/- 6 vs. 14 +/- 6 mm Hg), pulmonary capillary wedge pressure (28 +/- 7 vs. 31 +/- 10 mm Hg), serum sodium (136 +/- 7 vs. 139 +/- 6 mEq/L) and serum creatinine (1.7 +/- 0.8 vs. 1.8 +/- 1.8 mg/dL), were similar. The 6-month (51% vs. 18%) and 1-year (36% vs. 9%) survival rates were significantly higher (P = 0.001 for both) in group 1 than in group 2. In addition, patients treated with intermittent intravenous inotropic agents improved their functional and hemodynamic status.
Intermittent intravenous inotropic agents combined with prophylactic oral amiodarone seem to improve the outcomes of patients with end-stage chronic heart failure. Further research is warranted to elucidate whether this treatment strategy should be considered as a standard therapy in patients with refractory end-stage heart failure.
Journal of cardiovascular pharmacology 02/2009; 53(2):157-61. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When revascularization facilities are not available, thrombolytic therapy (TT) added to intra-aortic balloon counterpulsation (IABC) has been proposed as initial therapy for the management of patients presenting with postmyocardial infarction (MI) cardiogenic shock, followed by prompt transfer to another institution for revascularization. The use of TT in this setting, however, remains controversial.
We reviewed the records of 81 consecutive patients admitted with cardiogenic shock after acute MI and compared the outcomes of patients initially stabilized, including IABC as an adjunct to TT (IABC+TT group, n=40), with those patients initially stabilized with IABC and no TT (IABC group, n=41).
The baseline characteristics of the two study groups were similar. The in-hospital and 6-month survival rates were 47.5 and 33.3% in the IABC+TT group versus 43.9 and 31.6% in the IABC group, respectively (NS). Except for mechanical ventilation more frequently required in the IABC group, other outcome measures were similar in both groups. The in-hospital (76.5 vs. 36.5%, P=0.008) and 6-month (60 vs. 25.4%, P=0.01) survival rates were significantly higher in patients who underwent delayed invasive revascularization, than in patients who underwent no invasive revascularization attempt.
In patients presenting with acute MI and cardiogenic shock, TT as an adjunct to IABC added no therapeutic benefit when compared with IABC alone. In contrast, the survival of patients was significantly increased by delayed invasive revascularization in both treatment groups. These observations suggest that, when revascularization facilities are not available, stabilization with IABC, followed by prompt transfer for delayed revascularization to a tertiary care hospital, might be the preferred management strategy for patients presenting with post-MI cardiogenic shock.
[Show abstract][Hide abstract] ABSTRACT: Studies of the IABP have reported variable effects on coronary blood flow (CBF). The purpose of the present study was to measure the changes in coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation in normal and reperfused porcine myocardium.
A 30-ml IABP was placed in the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the mid-left anterior descending (LAD) coronary artery for 1 h, followed by reperfusion for 2 h. The effects of IABP support on systolic aortic pressure (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to the LAD occlusion site was measured at baseline and during reperfusion, with and without IABP counterpulsation.
The IABP decreased SAP and aortic end-diastolic pressure in normal and reperfused myocardium, and maintained a peak aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%, 12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the assistance of the IABP (all p<0.05).
In the normal heart, IABP counterpulsation decreased CBF, probably because of a decrease in myocardial oxygen demand from a decreased afterload. During reperfusion the IABP increased CBF, suggesting that it might effectively mitigate the no-reflow phenomenon.
International journal of cardiology 09/2008; 138(3):253-60. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ibutilide is a class III antiarrhythmic drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsades de pointes. Amiodarone is also used for the cardioversion of atrial fibrillation and prolongs the QT interval but rarely causes torsades de pointes.
The study included 51 consecutive patients with recent onset atrial fibrillation in whom the administration of ibutilide failed to restore sinus rhythm. In those patients we decided to proceed to intravenous administration of amiodarone. The QT intervals were measured on 12-lead ECG. After 11 +/- 5 h of the administration of the amiodarone, 42 patients (82%) were on sinus rhythm. There was no episode of non-sustained torsades de pointes or hypotension that followed the administration of the two antiarrhythmic agents.
The administration of amiodarone in the case of ibutilide failure may be a useful adjunct to current cardioversion protocols for recent onset atrial fibrillation.