Alexandros C. Kralios

Effect of Therapeutic Dopamine Administration on Myocardial Catecholamine and Neuropeptide Y Concentrations in the Failing Ventricles of Patients with Idiopathic Dilated Cardiomyopathy

Summary: The purpose of this study was to investigate the relationship between dopamine (DA) exposure and myocardial catecholamine and neuropeptide Y (NPY) concentrations in patients with severe congestive heart failure due to idiopathic dilated cardiomyopathy (IDC). Both nonfailing (NF) and failing (F) hearts were obtained in collaboration with the Utah Cardiac Transplantation Program and the Intermountain Organ Recovery System. The patients were stratified into five groups according to their preoperative exposure to dobutamine (DBT) and/or DA. Compared to 12 untreated, NF control hearts, norepinephrine (NE) concentrations were significantly decreased in 30 untreated F hearts obtained from patients with IDC. Norepinephrine concentrations were also significantly decreased in DA-treated NF hearts and in DAtreated F hearts compared to untreated NF and untreated or DBT-treated failing hearts, respectively. NPY concentrations were significantly decreased in untreated F hearts and were further decreased in dopamine-treated NF and DA-treated F hearts compared to untreated NF and untreated or DBT-treated F hearts. Thus, NE and NPY depletion related to DA administration was evident in both NF and F myocardium and was specific for DA in that it was not evident in patients who received the direct-acting β-agonist inotrope DBT. These data suggest that the major inotropic mechanism of action of DA is through cardiac adrenergic neurotransmitter release. The data also provide further support for the concept that indirect acting inotropes such as DA may have limited inotropic potential in F hearts where neuronal NE has been depleted

Relative effects of propranolol and timolol on ventricular fibrillation threshold and hemodynamics in the dog

The relationship between the antifibrillatory and hemodynamic effects of propranolol and timolol was tested in 32 dogs divided into three groups. In closed-chest animals (group 1), the maximal increase of the ventricular fibrillation threshold (VFT) from the control state was 67.3 +/- 22.6% (n = 5, p less than 0.01) for propranolol and 95.8 +/- 18.8% (n = 9, p less than 0.005) for timolol. These effects were paralleled by a decrease in the cardiac index of 34.7 +/- 10.2% (p less than 0.05) and 32.5 +/- 9.4% (p less than 0.02) for propranolol and timolol, respectively. The mean systemic arterial pressure (SAP) also decreased by 25.0 +/- 8.8% (p less than 0.05) and 19.2 +/- 5.1% (p less than 0.01). In open-chest animals (group 2), timolol increased the VFT by 86.6 +/- 27% (n = 5, p less than 0.05) and decreased the cardiac index by 57.3 +/- 6.3% (p less than 0.005) and the mean SAP by 28.5 +/- 2.9% (p less than 0.02). In open-chest animals with stabilized peripheral hemodynamics (group 3), VFT increased by 354 +/- 130% (p less than 0.05) and 437 +/- 144% (p less than 0.05) after the maximal administered doses of propranolol (n = 6) and timolol (n = 7), respectively. These results suggest that the electrophysiologic and hemodynamic effects of beta blockade are parallel and interdependent, with the hemodynamic deterioration markedly blunting the beneficial electrophysiologic effects.

Protective effect of coronary sinus obstruction from primary ischemia-induced ventricular fibrillation in the dog

We examined whether partial coronary sinus obstruction affects the latency of the early ventricular fibrillation (VF) of acute ischemia. During baseline trials 15 of 19 open-chest dogs fibrillated repeatedly and predictably within 2 to 5 minutes (251.6 +/- 64 seconds) after reversible, double coronary artery occlusion without developing profound hemodynamic deterioration. The effect of partial coronary sinus obstruction sufficient to increase coronary sinus pressure to 40 mm Hg could be adequately tested in 11 dogs. Coronary sinus obstruction consistently prevented VF in five dogs, significantly prolonged the VF latency in three (p < 0.01 to p < 0.001), and had no clear effect in another three. The overall effect was significant at the p < 0.01 level. VF latency prolongation/prevention was also positively correlated to the residual coronary sinus pressure at the time of VF (r = 0.76; p < 0.008), as well as the baseline VF latency (r = 0.75; (p < 0.008). The protective effect of coronary venous hypertension most likely reflects preservation of adequate extracellular fluid in the ischemic region after the perfusion arrest. This extracellular fluid may constitute a key component in the prevention of early ischemic arrhythmias by preserving interstitial hydraulic continuity and tissue homogeneity through enhanced dilution and diffusion of solutes.

Feasibility of Closed-Chest Left Ventricular Bypass Using Unilateral Retrograde Transpulmonary Flow

A method for closed-chest left heart bypass using retrograde unilateral transpulmonry blood flow originating from the left atrium and retrieved by a cuffed cannula wedged in a pulmonary artery branch is described. Technical feasibility and physiological implications were tested in 12 anesthetized sheep and 4 awake calves. Retrograde transpulmonary flow showed a curvilinear relationship to the left atrial pressure, with the highest rate of rise occurring when left atrial pressure approached levels of pulmonary edema (25 to 35 mm Hg); at this point retrograde transpulmonary flow became equal to control cardiac output. The intervention and the bypass were well tolerated for short periods by these healthy animals. The possible advantages of the method are discussed, with emphasis on self-regulation of bypass flow by the filling resistance of the left ventricle.