Abel F L, Wilson S P, Zhao R R, Fennell W H
Department of Physiology, University of South Carolina School of Medicine, Columbia 29208.
Circ Shock. 1989 Aug;28(4):309-19.
The effects of cocaine hydrochloride infusion on left ventricular function in the anesthetized dog were observed under controlled heart rate and blood pressure conditions. In every case an immediate decrease in performance, as evidenced by maximal + rate of change of ventricular pressure (dP/dt), occurred and was a linear function of cumulative dose. Maximal (-) dP/dt also declined, indicating a decreased rate of ventricular relaxation. Right atrial and left ventricular end diastolic pressure increased, with no change in cardiac output or cardiac work, whereas coronary flow decreased slightly. This small decrease in coronary flow was probably related to the decrease in contractile vigor rather than a direct effect of cocaine on vascular tone. Although plasma norepinephrine concentration initially increased, ventricular function did not increase and continued to decline with cumulative cocaine dose. Tissue norepinephrine levels measured in isolated heart-lung preparations were not depleted. These findings indicate a direct toxic action of cocaine on the myocardium, decreasing both contractile performance and relaxation state. Plasma cocaine levels were constant during continuous infusion of the drug, indicating that the progressive toxicity observed did not result from increased circulating cocaine.
在控制心率和血压的条件下，观察了盐酸可卡因输注对麻醉犬左心室功能的影响。在每种情况下，心室压力最大变化率（dP/dt）所显示的心脏功能立即下降，且是累积剂量的线性函数。最大（-）dP/dt也下降，表明心室舒张速率降低。右心房和左心室舒张末期压力升高，心输出量或心脏作功无变化，而冠状动脉血流量略有减少。冠状动脉血流量的这种小幅减少可能与收缩力下降有关，而非可卡因对血管张力的直接影响。虽然血浆去甲肾上腺素浓度最初升高，但心室功能并未增强，且随着可卡因累积剂量的增加而持续下降。在离体心肺制备物中测得的组织去甲肾上腺素水平并未耗尽。这些发现表明可卡因对心肌有直接毒性作用，会降低收缩性能和舒张状态。在持续输注药物期间，血浆可卡因水平保持恒定，表明观察到的渐进性毒性并非由循环中可卡因增加所致。
