Effects of Nitroglycerin and Dipyridamole on Myocardial Perfusion during Total and Graded Partial Coronary Occlusion in Open Chest Dogs

Hong, Young Kyu; Kim, Young Hoon; Park, Chang Gyu; Seo, Hong Seog; Shim, Wan Joo; Oh, Dong Joo; Ro, Young Moo

Abstract

BACKGROUND
To investigate the effects of nitroglycerin(NTG) and dipyridamoie(DIP) on the perfusion of ischemic myocardium during total occlusion of one coronary vessel and with 3 graded partial occlusion of its collateral supplying vessel, myocardial contrast echocardiography(MC-Echo) was performed on seven pentobarbital anesthetized open chest dogs.
METHODS
After a left thoracotomy was done, the left anterior descending coronary artery(LAD) was dissected for ligation to produce total LAD occlusion and left circumflex coronary artery(LCX) was separated to place an electromagnetic flow probe and, distally, screw occluder to restrict LCX flow by 50% and 90% of the preocclusion value. MC-Echo images were made by bolus injections of a 5ml of two-syringe-agitated mixture of sodium meglumine ioxaglate(Hexabrix) and normal saline(2 : 3 by volume) into the aortic root, and then the echocontrast defect area(EDA) with planimeter, peak echocontrast intensity(PEI) and the echocontrast washout halftime(WHT) with videodensitometer were measured. A 100microg of NTG was administered by bolus injection in the aortic root and was followed by 5mg of DIP after the hemodynamic effect of the NTG has been abolished. MC-Echo images were obtained after each infusion of NTG and DIP, first 60 minutes after total LAD occlusion with intact LCX flow, next with a 50% restriction of LCX flow, and third with a 90% restriction of LCX flow.
RESULTS
1) During total LAD occlusion with intact LCX flow : The EDA measured 60 minutes postocclusiom(PO) of LAD(14.2%) was smaller than that 3 minutes PO(20.5%, p<0.01). After NTG, systolic and diastolic blood pressure(BP) was decreased(p<0.01, p<0.05, respectively) and heart rate(HR) was not changed. The mean EDA(15.1%) was not changed, but an increase in EDA occurred in cases of which the diastolic BP fell by more than 20mmHg, and/or the systolic BP was less than 80mmHG after NTG, After DIP, BP and HR were unchanged. The PEI was increased and WHT was shortened in the nonischemic area, reflecting an increase in myocardial perfusion to a normal zone. However, the EDA(17.0%) was increased(p<0.05). The increase in EDA was more prominent in cases with good collaterals. This finding indicates that DIP cases coronary steal from the ischemic myocardium to the normal myocardium through the collaterals. 2) During total LAD occlusion with a 50% restriction of LCX flow : BP and HR were not altered. EDA, PEI and WHT were the same as those taken during intact LCX flow. After NTG, BP was decreased(p<0.01), but HR were not different from baseline values, After DIP, BP and HR remaince unchanged and EDA(16.2%) was increased(p<0.05). PEI was decreased(p<0.05) and WHT was delayed(p=0.054), indicating that DIP impaired any further increase of perfusion in ischemic myocardium. 3) During total LAD occlusion with a 90% restriction of LCX flow : Systolic and diastolic BP were decreased(p<0.05), but HR was unchanged. EDA(20.2%) was increased as compared to those during intact LCX flow(p<0.01). NTG decreased the EDA(17.6%, p<0.05) despite decrease in BP(p<0.01), while DIP did not alter the hemodynamics or EDA(20.7%). The PEI and WHT after infusion of both NTG and DIP were not different from baseline values.
CONCLUSION
1) Dipyridamole causes coronary steal from ischemic myocardium when the flow of collateral supplying vessel is intact or restricted by 50%, but not during 90% restriction of flow, suggesting the degree of stenosis of collateral supplying vessels is a determinant of coronary steal. 2) The beneficial effect of nitroglycerin to ischemic myocardium was largely determined by the extent of collateral flow and its effect on hemodynamics.