The major areas of normal coronary physiological research since Berne's 1964 review have been the measurement of ventricular transmural blood flow distribution with microspheres, the adenosine hypothesis of local metabolic control of coronary blood flow, and the autonomic control of coronary blood flow. There is an improved understanding of intramyocardial tissue pressure and extravascular compressive forces on coronary vessels. However, the unexpected finding of zero flow during a prolonged diastole with a coronary artery pressure of 40 mmHg (PZF) is a reminder that the physical forces, including vascular smooth muscle contraction, that determine coronary vascular resistance are incompletely understood. During normal circumstances, the left ventricular subendocardium probably receives more blood flow than the subepicardium does, but the difference is small. When the coronary circulation is compromised by stenosis or aortic valve lesions, the subendocardium is much more vulnerable to underperfusion than is the subepicardium. The coronary vasodilating effect of arterial hypoxia has been confirmed in many studies, but the role of tissue oxygen tension in local metabolic control of coronary blood flow during normoxia is unknown. The coronary vasodilating action of carbon dioxide has received renewed attention, but its role in local control is also unknown. The adenosine hypothesis has passed several critical tests, but despite much research the importance of adenosine in normal coronary regulation is not established. Local metabolic control of coronary blood flow probably involves more than just one factor, but a unified hypothesis has not been put forward. Sympathetic alpha-receptor-mediated coronary vasoconstriction has been demonstrated by nerve stimulation and during a carotid sinus baroreceptor reflex. Sympathetic coronary vasoconstriction is capable of competing with local metabolic control to lower coronary venous oxygen tension under experimental circumstances, but its importance during normal resting conditions is not established. Parasympathetic muscarinic coronary vasodilation has been shown by vagal nerve stimulation, but a role for it during normal blood flow regulation has yet to be demonstrated. There have been elegant descriptive studies of the coronary blood flow response during excitement and exercise, where coronary blood flow increases pari passu with myocardial metabolism; however, there are also data that indicate a concomitant sympathetic vasoconstrictor effect during strenuous exercise. Overall there has been encouraging progress in coronary physiology. Inevitably new knowledge has focused old questions and presented new ones.

Previously published and as yet unpublished QCD results obtained with the ALEPH detector at LEP1 are presented. The unprecedented statistics allows detailed studies of both perturbative and non-perturbative aspects of strong interactions to be carried out using hadronic Z and tau decays. The studies presented include precise determinations of the strong coupling constant, tests of its avour independence, tests of the SU(3) gauge structure of QCD, study of coherence eects, and measurements of single-particle inclusive distributions and two-particle correlations for many identied baryons and mesons.

Voltage-gated sodium channels composed of pore-forming ␣ and auxiliary ␤ subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of distinct sodium channel subtypes have not been clearly defined. Immunocytochemical studies show that the principal cardiac poreforming ␣ subunit isoform Nav1.5 is preferentially localized in intercalated disks, whereas the brain ␣ subunit isoforms Nav1.1, Nav1.3, and Nav1.6 are localized in the transverse tubules. Sodium currents due to the highly tetrodotoxin (TTX)-sensitive brain isoforms in the transverse tubules are small and are detectable only after activation with ␤ scorpion toxin. Nevertheless, they play an important role in coupling depolarization of the cell surface membrane to contraction, because low TTX concentrations reduce left ventricular function. Our results suggest that the principal cardiac isoform in the intercalated disks is primarily responsible for action potential conduction between cells and reveal an unexpected role for brain sodium channel isoforms in the transverse tubules in coupling electrical excitation to contraction in cardiac muscle.

At rest the myocardium extracts approximately 75% of the oxygen delivered by coronary blood flow. Thus there is little extraction reserve when myocardial oxygen consumption is augmented severalfold during exercise. There are local metabolic feedback and sympathetic feedforward control mechanisms that match coronary blood flow to myocardial oxygen consumption. Despite intensive research the local feedback control mechanism remains unknown. Physiological local metabolic control is not due to adenosine, ATP-dependent K(+) channels, nitric oxide, prostaglandins, or inhibition of endothelin. Adenosine and ATP-dependent K(+) channels are involved in pathophysiological ischemic or hypoxic coronary dilation and myocardial protection during ischemia. Sympathetic beta-adrenoceptor-mediated feedforward arteriolar vasodilation contributes approximately 25% of the increase in coronary blood flow during exercise. Sympathetic alpha-adrenoceptor-mediated vasoconstriction in medium and large coronary arteries during exercise helps maintain blood flow to the vulnerable subendocardium when cardiac contractility, heart rate, and myocardial oxygen consumption are high. In conclusion, several potential mediators of local metabolic control of the coronary circulation have been evaluated without success. More research is needed.

Background: Human plasma ATP concentration is reported in many studies as roughly 1000 nmol/L. The present study tested the hypothesis that the measured plasma ATP concentration is lower if ATP release from formed blood elements is inhibited during blood sample processing. A second hypothesis was that pretreatment with aspirin to inhibit platelets would reduce the measured plasma concentration of ATP.