Vasoactive parathyroid hormone in the treatment of acute ischemic left ventricular failure and the prevention of cardiogenic shock.
Molecular fragment 1-34 of synthetic bovine parathyroid hormone (bPTH[1-34]) has been found to be a potent coronary vasodilator, a moderate systemic vasodilator, and a positive inotropic agent for the myocardium. On that basis, the hypothesis was tested that "vasoactive" PTH might be effective in the treatment of acute ischemic left ventricular failure (LVF) and the prevention of cardiogenic shock. Dogs whose sympathetic nerve activity was blocked by a combination of reserpine, propranolol, and chlorpromazine were anesthetized and subjected to open-chest occlusion of the left anterior descending coronary artery (LAD) plus sequential ligation of three diagonal branches. In ten untreated animals (control group), acute myocardial ischemia led to LVF and, within 4 hours, to cardiogenic shock (50% or greater reduction in cardiac output; 30% or greater reduction in mean aortic pressure; elevation of left atrial pressure above 20 mm Hg; and significant elevation of arterial blood lactate concentration). At the end of 4 hours, myocardial infarction measured by the incubation of transverse slices of the left ventricle in TTC solution represented 96 +/- 3% of the myocardium "at risk." In ten treated animals (experimental group), PTH(1-34) was administered intravenously, 1 U/kg/min, starting 30 minutes after coronary occlusion. Treatment improved left coronary blood flow from 55 +/- 5 to 120 +/- 11 ml/100 g LV/min, increased cardiac index from 72.5 +/- 7 to 117.5 +/- 12 ml/kg/min, reduced left atrial pressure from 27.5 +/- 2.5 to 15 +/- 2.5 mm Hg (all changes, P less than 0.005), sustained aortic pressure, and prevented the elevation of arterial blood lactate. At the end of 4 hours, myocardial infarction represented 30 +/- 1.2% of the myocardium at risk (difference between the two groups significant, P less than 0.005). Thus, PTH(1-34) exerted a tissue-sparing effect on the myocardium, restored LV function, and prevented the development of shock.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D012770:Shock, Cardiogenic / Q000503:physiopathology / Q000517:prevention & control*; D019379:Teriparatide; D014655:Vascular Resistance / Q000187:drug effects
D007773:Lactates; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D019344:Lactic Acid