SUMMARY We employed intracoronary infusions of calf intenstine adenosine deaminase (ADA) to test the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia (RH). Infusions of 4.5 U ADA/min per kg body weight into the left circumflex coronary artery of 10 open-chest dogs reversibly reduced repayment of flow debt by 30-39% ( P < 0.05) following 5-, 10-, 15-, 20-, and 30-second coronary occlusions, the percentage reduction being independent of occlusion length. ADA reduced peak RH flow rate (17%, P < 0.05) only after 5-second occlusions. Intracoronary infusions of ["']ADA in seven dogs produced interstitial ADA concentrations between 1.2 and 13.1 U/ ml in perfused myocardium and, In five of these dogs, '"I activity in the cardiac node was 1.8-35 times that of contiguous mediastinal tissue. Theophylline, a specific adenosine antagonist, reduced repayment of flow debt by 27-38% {P < 0.02) in eight dogs, an effect similar to that of ADA, In six other dogs, ADA plus theophylline did not reduce RH flow debt repayment below that produced by ADA alone. This experiment confirms the contribution of adenosine to myocardial RH but shows that this nucleoside accounts for but a third of volume flow. Other, as yet unidentified, factors are collectively more important. Ore Res 49: 1383Res 49: -1267 TWO lines of evidence support the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia: (1) adenosine appears in coronary venous blood during reactive hyperemia in quantities paralleling the duration of the preceding ischemic interval (Rubio et al., 1969), and (2) coronary flow rate changes concordantly during reactive hyperemia with changes in myocardial adenosine content (Olsson et al., 1978).However, other evidence challenges this view. Methylxanthines strongly antagonize the coronary effects of exogenous adenoaine (Afonso, 1970), yet only modestly reduce the reactive hyperemic response (Bittar and Pauly, 1971;Juhran et al., 1971; Cumish et al., 1972;Eikens and Wilcken, 1977). Coronary occlusions of one heart beat or less have no detectable effect on myocardial metabolism, yet elicit hyperemic responses (Eikens and Wilcken, 1974; Schwartz et el, 1980). Other vasodilatory substances such as K + and CO 2 (or H + ) accumulate in ischemic hearts and also could participate in reactive hyperemia (Raberger et al., 1975;Case, 1976;Murray and Sparks, 1978).This study estimates the contribution of adenosine to canine myocardial reactive hyperemia by employing adenosine deaminase (ADA) to destroy adenosine in the cardiac interstitium. This enzyme reduces but does not abolish this response, confirming that adenosine contributes to, but is not solely responsible for, post-ischemic coronary vasodilation. MethodsHealthy mongrel dogs weighing 15.5-30 kg were anesthetized by sodium pentobarbital (30 mg/kg, iv) and artificially ventilated at rates maintaining arterial blood Poj and Pco 2 in the normal range (Feigl and D'Alecy, 1971). Catheters in the right femoral vein a...

A comparison of blood flow and myocardial O2 consumption (MVO2) in the right and left ventricles was made in 21 open-chest dogs. Simultaneous measurements were made of left anterior descending (LAD) and right coronary arterial blood flow and of O2 saturation in the coronary sinus and in from one to four anterior cardiac veins. Blood flow was greater in the LAD than in the right coronary artery, 87 +/- 5 vs. 46 +/- 3 ml.min-1.100 g-1. Similarly, the O2 saturation was 51 +/- 3% in the anterior cardiac veins and 40 +/- 1% in the coronary sinus. In a subset of seven dogs, the O2 saturation in blood from anterior cardiac veins varied substantially from vein to vein. The mean MVO2 was greater for the left than for the right ventricle, 8.6 +/- 1.4 vs. 4.0 +/- 0.3 ml O2.min-1,100 g-1. Increases in LAD flow with no increase in O2 extraction accounted for enhanced MVO2 of the left ventricle due to pacing, isoproterenol, or methoxamine. In contrast, pacing, isoproterenol, or constriction of the pulmonary artery increased MVO2 of the right ventricle by both augmented O2 extraction and a rise in right coronary blood flow. We conclude that right coronary arterial blood flow is lower per 100 g tissue and is less dependent on MVO2 than is LAD blood flow. The heterogeneity of O2 saturation in anterior cardiac veins suggests that regional differences in MVO2 may exist.

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Abolished Early Afterdepolarization by Nicorandil. We describe a 17-year-old boy with idiopathic long QT syndrome and repeated syncopal episodes. Early afterdepolarization (EAD) in the monophasic action potential (MAP) was demonstrated in the posterior septum of the left ventricle. Injection of the potassium channi'l opener nicorandil decreased KAO and shortened MAP duration. The syncopal episodes due to ventricular fihrillation disappeared after administration of the potassium channel opener.

Objective: To investigate factors predicting the development of outward remodelling of the carotid artery in patients with atherosclerosis. Design: 130 patients with carotid artery stenosis (15-85% of the vessel diameter) were divided into two groups, based on the presence or absence of outward remodelling of the sclerotic carotid segment on high resolution ultrasonography. Logistic regression analysis was used to evaluate the contribution of haemodynamic, laboratory, and clinical measurements on the development of remodelling, including age, sex, type of stenosis, extent of plaque, per cent diameter stenosis, underlying disease, selected drug treatment, and plasma concentrations of total cholesterol, high density lipoprotein cholesterol, triglyceride, and uric acid. Results: 64 patients (49%) had outward remodelling. Multivariate regression analysis showed that hypertension, the type of plaque, the thickness of the plaque, and the extent of stenosis were independent factors predicting remodelling. The odds ratios of hypertension, unstable shape of plaque, thickness of plaque, and the extent of the stenosis were 6.70, 3.02, 2.04, and 1.05, respectively. Other measurements did not contribute significantly to the estimation of remodelling. Conclusions: Compensatory enlargement of the vessel occurs in about 50% of carotid artery segments with a diameter stenosis of 15-85%. Hypertension and the shape of the plaque are major determinants of the development of outward remodelling. I t has become apparent that blood vessels can enlarge to accommodate atheromatous plaques, forestalling encroachment on the lumen and hence preserving distal flow. Glagov and colleagues were the first to describe this process in the left main coronary artery in necropsy specimens.1 The findings were confirmed clinically in femoral 2 and coronary arteries, 3 using intravascular and epicardial ultrasonography, and in the carotid artery by body surface ultrasonography. This "outward remodelling" consists of a spectrum of structural changes whereby the vascular wall responds to alterations in its haemodynamic environment. Smoking, 4 aging, 5 and hypercholesterolaemia 6 are also thought to be involved in the development of outward vascular enlargement. However, although attempts have been made to investigate the factors participating in compensatory vascular reconstruction, the mechanism of this type of remodelling remains obscure. Our aim in this study was to determine the prevalence of vascular remodelling and to investigate the factors leading to outward remodelling in the atherosclerotic carotid artery, using high resolution cross sectional ultrasonography. METHODS SubjectsThe study population consisted of 165 consecutive patients with 15-85% diameter stenosis of the carotid artery system, determined by B mode ultrasonographic examination. Exclusion criteria were as follows: a major attack of coronary or cerebrovascular disease within one month of the investigation; overt congestive heart failure; cardiogenic shock; loss of consciousness; si...