Cardiotoxicity of lead at various perfusate calcium concentrations: functional and metabolic responses of the perfused rat heart.
Equilibrated rat hearts were perfused for 60 min with a standard crystalloid buffer containing either 0.9, 1.8, 3.5, or 5.0 mM Ca with or without added lead (0.3 and 30 microM). Contractile tension (T), rate of tension development (dT/dt), electrocardiographic (EKG), His bundle electrographic (HBE) indices, heart rate (HR), preejection period (PEP), and coronary flow rate (CFR) were recorded as a function of perfusion time. Endpoint analyses of myocardial phosphatic metabolites were performed on heart perchloric acid extracts by standard phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopic techniques. The contractile activity and glycerol 3-phosphorylcholine content of the myocardium were found to vary directly as a function of the perfusate calcium concentration; however, except for a prolonged atrioventricular-His bundle conduction time detected in hearts treated with 0.9 mM Ca, the variable perfusate calcium concentrations were devoid of any other significant physiologic and metabolic effects. In contrast, perfusion of control equilibrated hearts with 30 microM lead significantly attenuated the positive, and exacerbated the negative, inotropic responses to elevated, and low perfusate calcium concentrations, respectively. Moreover, a secondary, time-dependent decline in myocardial contractile strength was also observed in response to this lead concentration, which was progressively more pronounced with each increment in the perfusate calcium concentration. The preejection period of ventricular systole was also prolonged in response to 30 microM lead; however, this effect was less pronounced at higher perfusate calcium concentrations. Hearts perfused with 30 microM lead were also characterized by significant prolongation in atrioventricular node and His bundle conduction time, reduced coronary flow rate, and decreased heart rate, irrespective of the perfusate calcium concentration. Hearts treated with 0.3 microM lead exhibited functional properties that were diminished, but still comparable to control hearts. Analysis of myocardial phosphatic metabolite amounts following 60 min of perfusion revealed a significant lead-induced reduction in the energy status of the heart. The combination of 5.0 mM calcium with either 0.3 or 30 microM lead resulted in significant disturbances in phosphoglyceride, glycolytic, and high-energy phosphate pathways. These findings suggest that the cardiotoxic actions of lead are linked to complex mechanisms that are partially related to an interference with calcium-dependent cellular processes.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004347:Drug Interactions; D004558:Electric Stimulation; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D007854:Lead / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats
D007854:Lead; D002118:Calcium