Nitric oxide improves transpulmonary vascular mechanics but does not change intrinsic right ventricular contractility in an acute respiratory distress syndrome model with permissive hypercapnia

Department of Surgery, Duke University, Durham, North Carolina, United States
Critical Care Medicine (Impact Factor: 6.31). 10/1996; 24(9):1554-61. DOI: 10.1097/00003246-199609000-00021
Source: PubMed


To test the hypothesis that in a swine model of acute respiratory distress syndrome (ARDS) with permissive hypercapnia, inhaled nitric oxide would improve transpulmonary vascular mechanics and right ventricular workload while not changing intrinsic right ventricular contractility.
Prospective, randomized, controlled laboratory trial.
University research laboratory.
Eleven swine (30 to 46 kg).
The swine were anesthetized, intubated, and paralyzed. After median sternotomy, pressure transducers were placed in the right ventricle, pulmonary artery, and left atrium. An ultrasonic flow probe was placed around the pulmonary artery. Ultrasonic dimension transducers were sutured onto the heart at the base, apex, left ventricle (anterior, posterior, free wall), and right ventricle (free wall). An additional transducer was placed in the interventricular septum. A surfactant depletion model of ARDS was created by saline lung lavage. Nitric oxide was administered at 2, 4, and 6 parts per million (ppm), in a random order, under the condition of permissive hypercapnia (Paco2 55 to 75 torr [7.3 to 10.0 kPa]).
We evaluated the pulmonary vascular and right ventricular effects of permissive hypercapnia, with and without inhaled nitric oxide, by measuring variables of transpulmonary vascular mechanics and right ventricular function. These variables included mean pulmonary arterial pressure, right ventricular total power, right ventricular stroke work, transpulmonary vascular efficiency, and right ventricular intrinsic contractility. Data were obtained after lung injury under the following conditions: a) normocapnia (Paco2 35 to 45 torr [4.7 to 6.0 kPa]) and nitric oxide at 0 ppm; b) hypercapnia and nitric oxide at 0 ppm; c) hypercapnia and nitric oxide at 2, 4, and 6 ppm; and d) repeat measurements with hypercapnia and nitric oxide at 0 ppm. In ARDS with permissive hypercapnia, inhaled nitric oxide therapy (2 to 6 ppm) improved transpulmonary vascular mechanics and right ventricular workload by lowering pulmonary arterial pressure (29.6 +/- 1.3 vs. 24.6 +/- 1.0 mm Hg, p = .0001), increasing transpulmonary vascular efficiency (13.9 +/- 0.5 vs. 16.1 +/- 0.7 L/W-min, p = .0001), decreasing right ventricular total power (142 +/- 9 vs. 115 +/- 9 mW, p = .001), and decreasing right ventricular stroke work (653 +/- 37 vs. 525 +/- 32 ergs x 10(3), p = .001). Inhaled nitric oxide did not change right ventricular contractility, as measured by preload-recruitable stroke work.
Inhaled nitric oxide ameliorated any negative effects of hypoxic and hypercapnic pulmonary vasoconstriction. The beneficial effects of inhaled nitric oxide are related to alterations in right ventricular afterload and not intrinsic right ventricular contractility. The improved cardiopulmonary effects of inhaled nitric oxide with permissive hypercapnia potentially expand the use of nitric oxide in ARDS and other conditions in which this strategy is employed.

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    • "( 1985 ) too reported no significant increase in end - diastolic volume and pressure in the RV immediately after acute pulmonary artery banding in pigs , indicating that there was probably no alteration to the passive diastolic compliance of the RV after acute moderate pressure loading . Now , focusing on the pulmonary vascular mechanics and right ventricular hydraulic power behavior during different forms of acute and moderate PH ( mechanical occlusion , embolism , oleic acid lung injury , hypoxia ) we can resumed that TVE decreased significantly ( Calvin , 1985 ; Fitzpatrick , 1990 ; Cheifetz , 1996 ; Maggiorini , 1998 ; Pagnamenta , 2000 ; Wauthy , 2004 ) , owing to the highly increase of Wtot and the maintenance of pulmonary flow . PVR and / or Zo were also increase between 30 and 160% . "
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    ABSTRACT: The physiological importance of the right ventricle (RV) has been underestimated in the past. Until fairly recently, RV failure was a relatively neglected medical condition. The RV was considered as a moderately passive conduit between the systemic and pulmonary circulations. This belief was supported by studies showing that complete destruction of the right ventricular free wall in dogs (Starr, 1943) or its substitution by a synthetic patch (Taquini, 1963) , had no detectable impairment on overall cardiac performance. However, investigations in the 1970s demonstrated that right ventricular dysfunction has significant haemodynamic and cardiac performance effects, as illustrated by Cohen et al in six patients following a myocardial infarction involving the RV (Cohen, 1974). The patients had severe hypotension, diminished peripheral perfusion and severely impaired pressure generation in the RV, with almost no pressure gradient from the right atrium to the pulmonary artery. About it, Furey et al. (1984) concluded that the essential function of the RV is not pulmonary perfusion, but keeping an acceptable low pressure in the systemic venous system (Furey, 1984). Right ventricular dysfunction is implicated in nearly 20% of all deaths associated with congestive heart failure (Lee, 1992). Nowadays, the right ventricular essential role is becoming increasingly evident in a wide variety of conditions. In various forms of congenital heart disease, the RV is directly or indirectly subjected to abnormal loading conditions, and consequently right ventricular function has been shown to be a major determinant of clinical outcome in these patients (Fogel, 1998). Right ventricular function is also important in patients with acquired heart disease. For example, right ventricular dysfunction has an important independent bearing on prognosis in chronic obstructive pulmonary disease (Burgess, 2002), and in patients with primary pulmonary hypertension (PH), mortality rate was reported to be most closely associated with right ventricular hemodynamic function (McLaughlin, 2004). Pulmonary thromboembolic disease and acute respiratory distress syndrome represent other cases in which right ventricular function plays an essential role. In addition to right-sided valvular disease in which the RV is obviously involved, the function of the RV may also be relevant in left-sided valvular disease (Nagel, 1996). In patients with mitral regurgitation, the attention is primarily focused on the left ventricle (LV), but when the insufficiency is severe the RV may also be affected and right ventricular function should be considered during clinical management and treatment (Borer, 2002). In a recent review, Goldstein (Goldstein, 2002) discussed the pathophysiology and management of right heart ischemia and indicated that the RV appears to be relatively resistant to infarction and may recover even after prolonged occlusion. However, patients with inferior myocardial infarction who have right ventricular involvement are clearly at increased risk of death, shock, and arrhythmias (Metha, 2001).
    Cardiovascular failure. Pathophysiological bases and management., Fourth edited by E.I.C Fischer; A. Juffé Stein; J.M. Balaguer, 01/2006: chapter 2: pages 35-91; Ediciones del Valle., ISBN: 9509591572
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    01/1970: pages 337-429;
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    ABSTRACT: In the setting of acute pulmonary artery hypertension, techniques to reduce right ventricular energy requirements may ameliorate cardiac failure and reduce morbidity and mortality. Inhaled nitric oxide, a selective pulmonary vasodilator, may be effective in the treatment of pulmonary artery hypertension, but its effects on cardiopulmonary interactions are poorly understood. We therefore developed a model of hypoxic pulmonary vasoconstriction that mimics the clinical syndrome of acute pulmonary hypertension. Inhaled nitric oxide was administered in concentrations of 20, 40, and 80 ppm. During hypoxic pulmonary vasoconstriction, the administration of nitric oxide resulted in a significant improvement in pulmonary vascular mechanics and a reduction in right ventricular afterload. These improvements were a result of selective vasodilation of small pulmonary vessels and more efficient blood flow through the pulmonary vascular bed (improved transpulmonary vascular efficiency). The right ventricular total power output diminished during the inhalation of nitric oxide, indicating a reduction in right ventricular energy requirements. The net result of nitric oxide administration was an increase in right ventricular efficiency. These data suggest that nitric oxide may be beneficial to the failing right ventricle by improving pulmonary vascular mechanics and right ventricular efficiency.
    Journal of Thoracic and Cardiovascular Surgery 07/1997; 113(6):1006-13. DOI:10.1016/S0022-5223(97)70285-X · 4.17 Impact Factor
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