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Publications (128)
Background
While the acute exposure to electronic cigarette (E-cig) vapor has been associated with an increase in blood pressure, the chronic effect of E-cig vapor on blood pressure compared to standard cigarette smoke has not been extensively studied. We determined the effect of E-cig exposure on blood pressure and other measures of cardiac functi...
Introduction: Fluctuations of heart rate, or heart rate variability (HRV), contain important information about autonomic functions and regulations of the cardiovascular system. Heart rate fragmentation (HRF) is an inter-beat interval dynamics approach (Front Physiol, 2017 PMID: 29184505) that enhances analysis of short-term HRV. HRF has shown consi...
Background: Ischemic stroke is associated with high mortality, morbidity and disability that significantly affects the quality of life of patients even in the current thrombolytic/thrombectomy era. The effect of empagliflozin (EMPA), a sodium glucose co-transporter 2 inhibitor on stroke is unknown.
Methods: Male SD rats were randomized into three g...
Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migrai...
Background
Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long‐term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The in...
Background
While the acute exposure to electronic cigarette (E-cig) vapor has been associated with an increase in blood pressure, the chronic effect of E-cig vapor on blood pressure compared to standard cigarette smoke has not been extensively studied. We determined the effect of E-cig exposure on blood pressure and other cardiac functional measure...
The effect of electronic cigarette (E-cig) vaping on cardiac and vascular function during the healing phase of myocardial infarction (MI), and post-MI remodeling was investigated. Sprague Dawley rats were subjected to left coronary artery ligation to induce MI. One week later, rats were randomized to receive either 12 weeks of exposure to purified...
The availability of a wide range of flavored e-cigarettes is one of the primary reasons for vaping initiation and persistent use among adolescents and young people. This plethora of flavors available on the market are crafted using different flavoring agents such as cinnamaldehyde, vanillin, benzaldehyde, ethyl maltol, menthol, and dimethylpyrazine...
Introduction: There is little information about the effect of electronic cigarette (e-C) exposure on the cardiovascular system in the setting of myocardial infarction (MI) and whether e-C’s could alter vascular or cardiac function during the healing phase of MI. We determine the effect of e-C on endothelial function, cardiac remodeling and function...
Background: There are no data available regarding the effects of chronic electronic cigarette (eC) exposure on inflammatory gene expressions after myocardial infarction (MI) and whether eC could alter blood counts and chemistries in this setting. We determined the effect of eC on expression of genes for inflammatory cytokines and receptors and bloo...
Introduction: Naltrindole (NTI) was cardioprotective in both ex-vivo (5μM) and in-vivo (7.5mg/kg) rat myocardial ischemia-reperfusion (MIR) models. Recently, we showed that NTI 50-200μM (~2-7.5mg/kg, in-vivo) attenuated phorbol ester-induced PMN superoxide release by a novel mechanism devoid of opioid receptors. We hypothesize that NTI exerts its c...
Background: While the acute exposure to electronic cigarette (e-C) vapor has been associated with an increase in blood pressure, the chronic effect of e-C vapor on blood pressure compared to standard cigarette smoke has not been extensively studied. We determined the effect of chronic e-C exposure versus standard cigarette smoke on blood pressure a...
Background
Myocardial infarction (MI) is one of the leading causes of death worldwide. It is well-accepted that early diagnosis followed by early reperfusion therapy significantly increases the MI survival. Diagnosis of acute MI is traditionally based on the presence of chest pain and ECG criteria. However, around 50% of the MIs are without chest p...
Purpose:
We investigated the effects of exposure to electronic cigarettes (E-cig) vapor on the sizes of the no-reflow and myocardial infarction regions, and cardiovascular function compared to exposure to purified air and standard cigarette smoke.
Methods and results:
Sprague Dawley rats (both male and female, 6 weeks old) were successfully expo...
Background:
Electronic cigarettes (eC) may not be entirely benign. There is a lack of data on the effect of a single acute exposure of eC vapor using various heating sources and power settings upon lung injury. The purpose of this study was to determine if an acute exposure with eC vapor heated with different heating elements and power levels indu...
Background: We determined whether mitochondrial protective agents, elamipretide and SBT-255, could limit myocardial infarct (MI) size and the no reflow phenomenon in a standardized rat model.
Methods and Results: Anesthetized rats were randomized into 3 groups (n = 15 in each group): (1) Saline control group; (2) Bolus dose of elamipretide (1 mg/kg...
Introduction: We have recently shown (Alavi et al. Circulation, (2021)144: A13745-A13745) that adverse effects of nicotine delivered chronically by electronic cigarette (EC) vapor or standard cigarettes on left ventricular systolic function can be captured using intrinsic frequency (IF) method applied on carotid waveforms. Here, we propose a hybrid...
Purpose: We investigated the effects of chronic exposure to electronic cigarettes (e-cig) on myocardial infarct size and the size of the no-reflow zone in a rat model of both sexes.
Methods and Results: Sprague Dawley rats (6 weeks old) were randomized to 4 exposure groups: (1) Purified air (n=16 male/16 female); (2) e-cig vapor with 15mg/mL nicoti...
Background: The impact of long-term electronic cigarettes (E-cig) vaping on cardiovascular function in rats were investigated.
Methods: Sprague Dawley rats (both sex, 6 weeks old) were randomly exposed to filtered air (n=32), E-cig with nicotine (E-cig Nic ⁺ , n=26), E-cig without nicotine (E-cig Nic ⁻ , n=26), or standard cigarette smoke (n=31). A...
Purpose:
The present study was to determine whether OP2113 could limit myocardial infarction size and the no-reflow phenomenon in a rat myocardial ischemia/reperfusion model.
Methods:
Rat heart-isolated mitochondria (RHM) were used to investigate mitochondrial respiration and mitochondrial reactive oxygen species (mtROS) generation both in norma...
Our recent studies uncovered a novel GABA signaling pathway in embryonic forebrain endothelial cells that works independently from neuronal GABA signaling and revealed that disruptions in endothelial GABAA receptor-GABA signaling from early embryonic stages can directly contribute to the origin of psychiatric disorders. In the GABAA receptor β3 sub...
Background: A new form of lung injury was described in electronic cigarette users beginning July 2019 with patients presenting with respiratory distress. The condition is known as E-cigarette (eC) or vaping product use associated lung injury or EVALI and was thought to be related to Vit E oils used to dilute cannabis. Whether a single acute exposur...
Introduction: lectronic cigarette (eC) or Vaping induced Lung Injury (EVALI) was first described in the summer of 2019 in patients presenting with acute respiratory distress. Several factors contributing to EVALI are suspected, including use of oil carriers, and heating and power elements. This study examined whether a single acute exposure to eC s...
Introduction: Intrinsic frequency (IF) method is a novel systems-based approach that uses a single uncalibrated arterial waveform for the analysis of the left ventricle (LV) and arterial function. In a recent Framingham Heart Study, it was shown that IFs derived from carotid waveforms predict incident of heart failure and composite cardiovascular d...
Introduction: Cardiovascular intrinsic frequency (IF) is a systems approach for the analysis of left ventricle (LV) function, arterial dynamics, and LV-arterial coupling. It was shown in a recent Framingham Heart Study (Hypertension 2021, 77(2):338-346) that higher values of the first IF (ω1) (derived from carotid pressure waveforms) are associated...
Aims
Cardiovascular intrinsic frequencies (IFs) are associated with cardiovascular health and disease, separately capturing the systolic and diastolic information contained in a single (uncalibrated) arterial waveform. Previous clinical investigations related to IF have been restricted to studying chronic conditions, and hence its applicability for...
Introduction: Intrinsic Frequency (IF) method is a recently developed systems-based method that extracts dynamics information about left ventricle function (LV), arterial dynamics, and the LV-arterial coupling from arterial waveforms. We have recently shown (Alavi et al. Circulation, 140 (2019), A12573-A12573) that IF can detect occurrence of an ac...
Background: We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI).
Methods: After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion follo...
Introduction: Nicotine is a major bioactive component in tobacco cigarettes and electronic cigarettes. Despite the fact that smokers are at higher risk of experiencing an acute myocardial infarction (AMI), there are few studies that have examined the acute effects of nicotine on AMI.To address this issue, our present study was to examine the acute...
Background: Despite advances in early reperfusion therapy for acute ST elevation myocardial infarction (MI), mortality rates and prevention of heart failure after the MI are not optimal. There have been many attempts to further reduce the size of acute MI and to limit the no reflow phenomenon after reperfusion, with mixed results. One promising app...
Background: We investigated the effects of chronic electronic cigarettes with nicotine (E-Cig) exposure on cardiovascular function in rats.
Methods: Adult Sprague Dawley rats were exposed to either pure air (n=10) or E-Cig (n=14) for 12 weeks. After 12 weeks of exposure, flow-mediated vasodilation was measured in anesthetized rats with ultrasound t...
Aims
We investigated the acute effects of nicotine on myocardial infarct size, no reflow, hemodynamics and cardiac function in an acute myocardial ischemia and reperfusion infarction rat model.
Main methods
Female Sprague-Dawley rats (n = 23/group) received an intravenous loading dose of nicotine at 2.0 μg/kg/min or saline control for 30 min befor...
E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested...
We tested the hypothesis that therapeutic hypothermia (TH) improves survival and blunts inflammation in rats undergoing experimental hemorrhagic shock. Rats were randomized to TH (n = 16) or normothermia (n = 15). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure (MBP) of 30 mmHg for 30 minutes followed by reinfusion...
Background
We investigated whether the cardioprotective, volatile gas anesthetic agent, isoflurane, could improve survival and organ function from hemorrhagic shock in an experimental rat model, compared to standard nonvolatile anesthetic agent ketamine/xylazine.
Methods
Sprague Dawley rats (both genders) were randomized to receive either intraper...
Remote ischemic conditioning is the phenomenon whereby brief, nonlethal episodes of ischemia in one organ (such as a limb) protect a remote organ from ischemic necrosis induced by a longer duration of severe ischemia followed by reperfusion. This phenomenon has been reproduced by dozens of experimental laboratories and was shown to reduce the size...
Background: Recent studies by our group indicate that preconditioning, therapeutic hypothermia (TH) and TH combined with preconditioning improved long-term survival during resuscitation of hemorrhagic shock. The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation associated with increased mortality in patients with severe hemorrhage sh...
Background: We investigated the effects of hypothermia treatment alone and in combination with experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Previously we showed that RIPC alone improved survival.
Methods: In the hypothermia alone study, adult Sprague Dawley rats (both ge...
Background: Our research group recently observed that therapeutic hypothermia (TH) compared with normothermia improved long-term survival in an experimental model of hemorrhagic shock. The effect of TH on blood counts, blood gases and chemistries during the early phase of recovery from hemorrhagic shock are unknown. Therefore, the purpose of the pr...
Introduction: We recently introduced a novel systems-based approach, the Intrinsic Frequency (IF) method, for noninvasive evaluation of the cardiovascular dynamics using non-calibrated arterial pressure waveforms. In a recent clinical study, it was shown that left ventricle ejection fraction (systolic function) can be accurately computed from a sta...
Purpose
We investigated whether bilateral, lower limb remote ischemic preconditioning (RIPC) improved long-term survival using a rat model of hemorrhagic shock/resuscitation.
Methods
Rats were anesthetized, intubated and ventilated, and randomly assigned to RIPC, induced by inflating bilateral pressure cuffs around the femoral arteries to 200 mmHg...
Aims:
The purpose of the study was to determine whether late therapeutic hypothermia (LTH), administered after reperfusion, could prevent adverse left ventricular (LV) remodeling and improve cardiac function in the rat myocardial ischemia/reperfusion model.
Main methods:
Rats were randomized to normothermia (n = 10) or LTH (initiated at 1 min af...
Background: Recent studies in our laboratory indicate that isoflurane (ISO) has protective properties including improved survival in rats with hemorrhagic shock compared to ketamine and xylazine (K/X) anesthesia. The effects of these two anesthetic agents upon blood counts, gases and chemistries in the setting of hemorrhagic shock is unknown. The p...
Background: We investigated the cardiovascular responses to acute bleeding and shed blood restoration under different anesthetic agents, and their effects on long-term survival rate after hemorrhagic shock in rats, after our initial pilot study suggested differences between anesthetics.
Methods: Sprague Dawley rats (both genders) were randomized to...
Background: We further examined the protective effects of experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock.
Methods: Sprague Dawley rats (both genders) were randomized into RIPC (n= 26) or control group (n= 27), and anesthetized with intraperitoneal ketamine/xylazine. RIPC wa...
Background
We investigated whether bilateral lower limb remote ischemic preconditioning (RIP) could improve long‐term survival in a rat model of hemorrhagic shock/resuscitation.
Methods
Sprague Dawley rats (both genders) were anesthetized with intraperitoneal ketamine and xylazine, and were intubated and ventilated with room air. Rats were randoml...
Background
Hemorrhagic shock remains a major cause of mortality and morbidity on the battle field. Appropriate use of blood‐based biomarkers is clinically important to manage patients and predict death versus survival in the early stage of hemorrhagic shock. In continuation of our previous study, blood‐based early biomarkers were tested in 94 rats...
Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse...
Therapeutic hypothermia (TH) is known to protect against ischemia/reperfusion (I/R) injury. One mechanism of I/R injury includes secondary injury due to the inflammatory cascade. We hypothesized that TH reduces the inflammatory response following I/R injury. Rats were randomized to sham, normothermic, or hypothermic groups and subjected to 1 hour o...
The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agen...
Background:
Adjunctive therapies, given in addition to reperfusion to reduce myocardial infarct size, have been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. The no-reflow phenomenon occurs commonly after the infarct-related coronary artery is opened and predicts poor clinical...
PurposeDysfunctional mitochondria are considered to be the major source of intracellular reactive oxygen species and play a central role in the pathophysiology of myocardial ischemia/reperfusion. This study sought to determine effects of mitochondria-targeted cytoprotective peptide SBT-20 on myocardial infarct size in two different models of ischem...
The authors present the first in vivo measurements of L-Glucose and D-Glucose concentrations using millimeter waves. Employing direct injection of solutions into the rat jugular vein, we have been able to correlate immediate changes in blood glucose readings with transmission loss through the ears of anesthetized rats at Ka band (27–40 GHz). The se...
While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent...
This study sought to determine effects of SS20 on myocardial infarct size in two different models of ischemia/reperfusion. For in vivo studies, Anesthetized Sprague Dawley rats were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Rats were randomized to control group (received saline infusion), low dose SS‐2...
Aims:
We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondr...
Background-—The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model.
Methods and Results-—Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes co...
Introduction:
Although hypothermia reduces myocardial infarct size, noninvasive and rapid cooling methods are lacking. This study tests the effectiveness of a novel cooling apparatus on myocardial infarct size and no-reflow area in 2 models of coronary artery occlusion (CAO).
Methods and results:
Animals were randomized to normothermic (N) or hy...
Current therapies for myocardial infarction are geared to try to limit ischemic/reperfusion injury by early and complete reperfusion, including percutaneous coronary interventions, antiplatelet agents, and anticoagulants; and attempts to limit post infarction left ventricular remodeling by inhibitors of the renin-angiotensin-aldosterone pathway or...
Although preconditioning remains one of the most powerful maneuvers to reduce myocardial infarct size, it is not feasible in the clinical setting to pretreat patients prior to acute myocardial infarction (MI). The purpose of this study was to investigate the effect of more clinically relevant therapies of remote perconditioning, postconditioning, a...
A door-to-balloon time of less than 90 minutes is the gold standard for reperfusion therapy to treat acute myocardial infarction (MI). Because 30-day mortality remains ∼10%, new methods must be cultivated to limit myocardial injury. Therapeutic hypothermia has long been experimentally used to attenuate myocardial necrosis during MI with promising r...
: We evaluated the post-myocardial infarction (MI) therapeutic effects of Bendavia. Two hours after coronary artery ligation, rats were randomized to receive chronic Bendavia treatment (n=28) or water (n=26). Six weeks later, Bendavia significantly reduced scar circumference (39.7 ± 2.2 %) compared to water treatment (47.4 ± 0.03 %, p=0.024); and r...
Although numerous studies demonstrated that localized delivery of either cells or biomaterials improved postinfarction cardiac function, the underlying mechanisms for this effect remain unclear. We performed a comparison of the effects of fetal, neonatal, and human embryonic stem cell-derived cardiac cell as well as mesenchymal stem cell transplant...
Background
Our objectives were to characterize functional and structural features of an experimental model of Takotsubo cardiomyopathy, and its response to beta‐blockers.
Methods and Results
In protocol 1, a dose‐finding study: 69 rats received various doses of isoproterenol (ISO) and echocardiographic and histologic parameters were measured on da...
Background: While hypothermia reduces myocardial infarct size, non‐invasive and rapid cooling methods are lacking. This study tests the effectiveness of a novel cooling apparatus on myocardial infarct size and no‐reflow area in two models of coronary artery occlusion (CAO).
Methods and Results: Anesthetized rabbits (protocol 1) and anesthetized rat...
Bendavia is a mitochondrial‐targeting peptide with cardioprotective properties. Apoptosis and cardiac fibrosis contribute to left ventricular remodeling in the post infarct state. We hypothesized that Bendavia decreases apoptosis and attenuates myocardial collagen deposition in the noninfarcted border zone (2 mm noninfarcted tissue on either side o...
Objective: The purpose of our study was to assess the characteristics and time course of functional and histological abnormalities in an experimental model of Takotsubo Cardiomyopathy (TC).
Methods: Male Sprague‐Dawley rats were injected subcutaneously with either a single or two doses (at 24hrs interval) of isoproterenol (ISO; 25‐300 mg/kg). Echoc...
Bendavia (Ben), a mitochondria‐targeting peptide, protects mitochondrial function by enhancing bioenergetics under conditions of oxidative stress, thus inhibiting ROS formation. We hypothesized that Ben therapy would benefit post‐myocardial infarction (MI) cardiac function and remodeling in rats. At 2 hours after left coronary ligation, rats were r...
Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hy...
