Influence of the ischemic coronary bed on collateral blood flow.

The purpose of this study was to determine the influence of the resistance of the terminal vascular bed of an occluded coronary artery on collateral blood flow and collateral resistance. In 6 anesthetized dogs, left anterior descending coronary artery (LAD) was ligated, cannulated, and the terminal vascular bed was occluded by latex microspheres (diameter: 25 mu). Retrograde flow was measured using a new technique, which allowed control of outflow pressure of retrograde flow (PRF) at the LAD cannula. When retrograde flow was interrupted, pressure in the occluded vessel represented collateral perfusion pressure (CPP) within the border zone of the ischemic vessel. Collateral resistance was determined dividing the pressure difference across the collateral bed (CPP-PRF) by retrograde flow. Variation of PRF was used as a model for changes in resistance of the ischemic bed. Retrograde flow fell when PRF was increased from 11.0 +/- 3.0 ml X min-1 X 100 g-1 (PRF = 0) to 8.3 +/- 2.4 (p less than 0.01)(PRF = 24.6 +/- 6 mm Hg). For the same PRF range, collateral resistance fell from 9.68 +/- 2.96 to 8.30 +/- 2.50 mm Hg X ml-1 X min X 100 g (p less than 0.01). These results indicate that the vascular resistance of the terminal ischemic bed may considerably influence collateral blood flow and resistance.

On the range of alpha-adrenergic regulation of coronary vascular resistance.

In order to obtain an estimate of the range of alpha-adrenergic resistance regulation in the coronary vascular system, the following studies were performed: in 15 anesthetized dogs the circumflex coronary artery was cannulated and perfused with above-normal constant pressure to that coronary venous oxygen tension never fell below 40 mmHg. Thus, it was possible to eliminate the influence of the metabolic factor regulating coronary resistance. Furthermore, 15 isolated isovolumetrically working guinea-pig hearts were perfused according to the Langendorff method. Stimulation, resp. blockade, of alpha-receptors was achieved by administering xylometazoline, resp. phentolamine. Xylometazoline increased coronary resistance in both the isolated and the in-situ heart. Administering maximum doses to the anesthetized dog led to an increase in resistance to about 200%. This is equivalent to a reduction of conductance to about 50%. Phentolamine produced no significant effects in the isolated heart. Maximum dosage administered to the heart in situ led to a resistance decrease to about 60%, equivalent to an elevation of conductance to about 170%. If we let control values of coronary resistance and conductance be equal to 100%, our experiments showed alpha-adrenergic regulation of coronary resistance to range from about 60% to 200% and conductance to range from about 50% to 170%.

The dependence of coronary collateral blood flow on regional vascular resistances. Pharmacological studies with glyceryl trinitrate, adenosine and verapamil.

A method was applied in anesthetized dogs enabling the measurement of regional resistances up to and behind the start of collaterals and the collateral resistance. The studies show that peripheral coronary pressure, i.e. perfusion pressure of the collaterals, can change when the ratio of pre- and post-collateral resistance alters. Drugs can influence collateral blood flow not only by directly effecting the collaterals but also by altering collateral perfusion pressure. Glyceryl trinitrate given in minor doses improved collateral blood flow by directly dilating the collaterals and also by increasing collateral perfusion pressure. Higher doses did not improve collateral flow due to a decrease of collateral perfusion pressure. A steal-phenomenon occurred in some cases. Adenosine and verapamil had no direct influence on the collateral resistance. Verapamil given in small doses increased perfusion pressure slightly but not enough to improve collateral blood flow. High doses of verapamil, like low doses of adenosine, had no significant influence on collateral perfusion pressure and collateral blood flow. Adenosine given in high dosage led to a diminution of collateral flow by decreasing collateral perfusion pressure, i.e. a steal-phenomenon.

Pharmacological alterations of coronary collateral circulation; implication to the steal-phenomenon.

Measurements of resistances were performed on different parts of coronary vessels, including spontaneous collaterals in anesthetized dogs, following ligation and embolization of the descending branch of the left coronary artery. The normal situation was compared with the state of maximal pharmacological dilatation. The pharmacological dilatation decreased the collateral resistance by 24% in spite of the fact that the collaterals supplied an infarcted area in this case; the precollateral resistance, which chiefly consists of large vessels was also diminished. The collateral perfusion pressure is not only dependent on the aortic pressure, but also on the flow rate in the corresponding large coronary vessel and thereby on the ratio of precollateral to postcollateal resistance. A decrease of the collateral perfusion pressure causes an insufficient perfusion of the area supplied by the collaterals only when the pressure fall is not compensated for by an adequate decrease in the collateral resistance and when the ratio of the collateral to the nutritive resistance increases. Thus, both, the extent of the pressure fall across the precollateral resistance and the dilating capacity of the collaterals determine whether is not a pharmacological dilatation of the coronary vascular bed results in an insufficient supply of an infarcted area, i.e. in a so called "Steal-phenomenon". The results show further, that the given physical model of the microcirculation satisfactorily approximates the observed behaviour of the vascular system.

Comparative study of nitroglycerin and molsidomine. Effects on the integrated systemic venous bed and the arterial pressure in dogs.

The effect of nitroglycerin, N-carboxy-3-morpholino-sydnonimine-ethylester (molsidomine, Corvaton), and its metabolite 3-morpholinosydnonimine upon the peripheral circulation was investigated in 38 dogs with cardio-pulmonary bypass. The three compounds increased the integrated systemic venous blood volume and decreased the mean arterial pressure. The time course of the action of nitroglycerin was different from that of molsidomine: The arterial and venous effects of nitroglycerin began immediately after the injection was started, reached a maximum, and had disappeared after 7 min. The effects of molsidomine started later and showed no tendency to decrease during the observation period of 30 min. When referred to the same decrease in arterial blood pressure, molsidomine acted more strongly upon the systemic venous bed than did nitroglycerin. The arterial and venous effects of the molsidomine metabolite could be antagonized by a dopamine infusion. It is concluded that the hypotensive effect of the three compounds observed in the intact circulation is due to the diminuation of peripheral resistance as well as to the dilatation of the systemic venous bed. The dilatation of the veins effects a decrease in the venous return and thereby in the cardiac output and the arterial pressure. It can be concluded that the antianginal effect of the three compounds is not only due to the diminution of the afterload of the heart; the diminution of the heart; the diminution of the preload also represents an important component of action.