Coronary vasoactivity of adenosine in the conscious dog.

Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.

An implantable semiconductor beta-radiation detector.

An implantable beta-radiation detector suitable for the measurement of reginal blood flow in the experimental animal by the indicator clearance principle is described. A lithium-drifted silicon diode encapsulated in a stainless steel case is sutured over the site of interest. A suitable beta-emitting isotope, such as 85Kr in saline solution, is injected into the arterial supply and its calibrated against a mechanical system and showed excellent agreement up to 600 ml/100 g per min. At very high rates beyond the physiological range, flow was underestimated by a maximum of 10%. In vivo comparisons of myocardial blood flow assessed by the beta detector did not agree well with estimates of flow from a precordial counter or by the microsphere technique. Possible reasons are spatial heterogeneity of regional myocardial blood flow, the greatly different masses of tissue involved, or our inability to achieve sufficient numbers of spheres for accuracy in a 50-mg mass of tissue. The unit was still functional after 50 days in a chronic animal.

Phasic right coronary artery blood flow in conscious dogs with normal and elevated right ventricular pressures.

We studied phasic right coronary blood flow in well trained normal dogs and dogs with pulmonic stenosis. We installed electromagnetic flow transducers and pressure tubes under anesthesia to monitor right coronary blood flow, cardiac output, central aortic blood pressure, and right ventribular pressure. In normotensive dogs, systolic flow amplitude equaled early diastolic flow levels. The ratio of systolic to diastolic flow at rest was substantially greater in the right coronary bed (36+/-1.3%) than in the left circumflex bed (13+/-3.6%). Right diastolid flow runoff, including the cove late in diastole, resembled left circumflex runoff. Blood flow to the normotensive right (37+/-1.1 ml/min 100(-1) g) and the left (35+/-1.0 ml/min(-1) g) ventricular myocardium indicated equal perfusion of both cardiac walls. Throttling of systolic flow was related directly to the right ventricular systolic pressure level in the dogs with pulmonic stenosis. Retrograde systolic flow occurred in severe right ventricular hypertension. The late diastolic runoff pattern in dogs with pulmonic stenosis appeared the same as for the normotensive dogs. We obtained systolic to diastolic flow ratios of 1/3 the value of normotensive hearts in high and severe pulmonic hypertension. Electrocardiograms and studies of pathology suggested restricted blood flow to the inner layers of the right myocardium in the dogs with severe and high right ventricular hypertension. Normotensive and hypertensive peak hyperemic flow responses were similar, except for an increased magnitude of diastolic flow, with proportionately less systolic flow in hypertensive states.

Evidence for an adenosine receptor on the surface of dog coronary myocytes.

Adenosine and theophylline were linked covalently to oxidized stachyose to produce compounds too large to penetrate cell membranes. These compounds were used in two conscious and six open-chest anesthetized dogs to test the hypothesis that there is an adenosine receptor on the surface of the coronary myocyte. Intracoronary infusions of the adenosine derivative produced dose-dependent coronary vasodilation which was antagonized by theophylline; two types of theophylline derivative antagonized the coronary vasodilatory action of adenosine. Although these results show that both adenosine and theophylline exert their coronary effects at the surface of the smooth muscle cells, this evidence does not establish that they are competing for a common receptor.