Cardioscience最新文献

The RR interval, i.e. the heart period (T), increases with body mass (M) as: T = T0M0.27. The characteristic time of the arterial system (arterial decay time or decay time of aortic pressure in diastole, tau) equals peripheral resistance times total arterial compliance. Peripheral resistance equals mean systemic pressure over cardiac output. It can be derived that total arterial compliance is proportional to cardiac output times aortic length. Because mean aortic pressure is similar in different mammals the arterial decay time is proportional to the length of the aorta. Since aortic length and body length are related to body mass with the same exponent it follows that the arterial decay time is proportional to body length. It was found that the arterial decay time is related to body mass as tau = tau oM0.29. The heart period and the duration of diastole have similar exponents. We suggest that the heart period is matched to the arterial decay time to provide similar conditions for coronary perfusion. Since the arterial decay time is proportional to body length, heart period is also proportional to body length.

Classic ischemic preconditioning confers protection to the vulnerable myocardium following brief periods of ischemia with short intermittent periods of reperfusion. The aims of this study were: (i) to ascertain the protection from preconditioning using a relatively long reperfusion interval; (ii) to see whether this protection exists if preconditioning and long reperfusion is repeated and (iii) to evaluate the effect that an additional preconditioning stimulus has if it is given immediately before the sustained ischemia. Following anesthesia, in-vivo hearts were preconditioned with a 5 minute coronary ligation followed by 10 minutes reperfusion (Group A). This was compared to groups that were preconditioned with 5 minutes ischemia and 1 hour reperfusion (Group B); or 5 minutes ischemia with 1 hour reperfusion, repeated twice (Group C); or 5 minutes ischemia with 1 hour reperfusion repeated twice and followed by 5 minutes ischemia and 10 minutes reperfusion (Group D). Protection was assessed by subjecting each of the above groups to a further 45 minutes of regional ischemia followed by 120 minutes reperfusion. This protocol without prior preconditioning served as a control (Group E). The ratio of the infarcted to risk area was 23.1 +/- 4.1% in group A, 38.3 +/- 3.5% in group B, 58.4 +/- 4.9% in group C, 10.4 +/- 3.1% in group D and 61.8 +/- 6.2% in the control group E. Group D was significantly different from all the other groups. Group B was not different in comparison to the control group E. When a relatively long reperfusion period (Group B) was introduced the preconditioning protection diminished. When this long reperfusion period was repeated (Group C) overall protection was lost. However, when preconditioning was re-introduced alter a long delay (Group D), the protection afforded by it not only returned but appeared to be potentiated.

It has recently been shown that distension of the stomach in anesthetized pigs causes reflex hemodynamic responses through efferent sympathetic mechanisms. The present study was undertaken to investigate whether these mechanisms include activation of the renin-angiotensin system. In twelve anesthetized pigs, intragastric balloons were distended for periods of 30 minutes by 0.81 of warm Ringer solution (mean gastric transmural pressure of about 12 mmHg). Changes in arterial blood pressure and heart rate were respectively prevented by a pressurized reservoir connected to the left femoral artery and by atrial pacing. Plasma renin activity was measured during the last minute of distension by radioimmunoassay of angiotensin I. In each of the twelve pigs distension of the stomach caused an increase in plasma renin activity. In five pigs, this response was graded with step increments of the distension. The increase in plasma renin activity to gastric distension was abolished by bilateral subdiaphragmatic vagotomy (six pigs) and by bilateral section of the renal nerves (six pigs). The present study showed that innocuous distension of the stomach in the anesthetized pig reflexly increased plasma renin activity. The afferent limb of the reflex was in the vagal nerves and the efferent limb involved renal nerves.

The role of neuropeptide Y (NPY) in the regulation of cardiac function was compared in mammalian and fish hearts. In mammalian heart, most studies have shown that neuropeptide Y inhibits coronary flow and exerts a negative inotropic effect in isolated perfused hearts and cardiac muscles. The mechanisms involved in the action of neuropeptide Y in the heart are under active investigation. Our studies have shown that [Leu31,Pro34]NPY. NPY13-36, neuropeptide Y and peptide YY induced a concentration-dependent decrease in inositol 1,4,5-trisphosphate levels in rat cardiomyocytes, which was blocked by neuropeptide Y antagonists NPY18-36 or PYX-2. There is no difference in the inhibitory effect of neuropeptide Y and peptide YY on inositol 1,4,5-trisphosphate formation. Furthermore, the effects of neuropeptide Y and its analogues were insensitive to pertussis toxin pretreatment. These observations indicate that Y1 and Y2 subtypes of neuropeptide Y receptor in rat cardiomyocytes may be associated with inositol 1,4,5-trisphosphate formation through a pertussis toxin-insensitive Gq protein. The decreased formation of inositol 1,4,5-trisphosphate may be implicated in the negative inotropic effect of neuropeptide Y in the mammalian heart. In dogfish hearts, on the other hand, neuropeptide Y increased cardiac output by increasing heart rate, whereas norepinephrine increased cardiac output by increasing stroke volume. Although neuropeptide Y or norepinephrine alone did not have significant effects on pressure development in these hearts, neuropeptide Y plus norepinephrine did increase pressure development. The inositol 1,4-5-triphosphate level was elevated by norepinephrine alone and was further increased by neuropeptide y plus norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

St Thomas' Hospital cardioplegic solution is commonly used to arrest hearts during surgery. Pursuing the hypothesis that the cardioprotective properties of adenosine could be a beneficial adjunct to a solution containing high K+ and Mg2+, we tested a low and a high adenosine concentration added to this cardioplegic solution, aiming at improved recovery of function and energy status. We arrested 18 working rat hearts by a 3-minute infusion with the solution without or with 50 microM or 5 mM adenosine. We induced 30 minute stop-flow ischemia at 37 degrees C, followed by 10 minute washout (Langendorff mode) and 20 minute reperfusion (working heart). Control cardioplegia induced electrical arrest in 19.8 +/- 5.5 s. This took 9.1 +/- 0.9* and 12.7 +/- 1.8 s in the presence of 50 microM and 5 mM adenosine, respectively (*p < 0.05 vs no adenosine). During reperfusion a regular electrocardiogram appeared after 1.9 +/- 0.3 minutes in controls, after 1.0 +/- 0.0* and 1.7 +/- 0.2 minutes in hearts treated with low and high-dose adenosine, respectively (*p < 0.05 vs no adenosine). After 20 minute reperfusion, the pressure-rate product had recovered to 65 +/- 17% in controls, and to 107 +/- 11** and 72 +/- 11% of preischemic values in hearts treated with 50 microM and 5 mM adenosine, respectively (**p < 0.05 vs other groups). There was a good correlation between reperfusion function recovery and the postischemic release of creatine kinase, an index for irreversible cellular damage. This association was absent with ATP content, which increased with the adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Natriuretic peptides are hormones that play an important role in the cardiovascular control of mammalian and non-mammalian vertebrates. They have been classified into four groups. Of these, ANP (atrial natriuretic peptide), BNP (brain atriuretic peptides), CNP (C-type natriuretic peptide) are detected in cardiac and non cardiac tissues of all vertebrates; while VNP (ventricular natriuretic peptide) has been isolated only from the fish ventricle. All peptides have shown a high degree of sequence homology. The expression of the three principal types of natriuretic peptide (ANP, BNP and CNP) in cardiac tissues is developmentally and functionally regulated in a highly tissue-specific manner. Three types of natriuretic peptide receptors have been identified in numerous target tissues. Two receptors are transmembrane guanylyl cyclases (ANPR-A and ANPR-B) that mediate biological effects of natriuretic peptides; the third one (ANPR-C) has no guanylyl cyclase and is called "clearance receptor." The presence of natriuretic peptide binding sites in the heart suggests new aspects of paracrine control of cardiac function. A relevant localization of natriuretic peptide receptors was found in those cardiac regions particularly suitable for monitoring blood volume and pressure oscillations such as the inflow tract and the outflow tract. For example, in birds (quail) the highest levels of natriuretic peptide receptors were detected in the inflow tract represented by the vena cava. In both fish and birds, the outflow chamber, the bulbus cordis, had a high number of natriuretic peptide binding sites. In mammals, a remarkable concentration of natriuretic peptide receptors was also observed in the coronary vessels. This zoning of cardiac natriuretic peptide receptors indicates an intracardiac action of the hormones and adds a humoral dimension to the morphofunctional design of the vertebrate heart.

We have studied the cardiac development of the dogfish (Scyliorhinus canicula) in six serially sectioned embryos ranging from 14 to 40 mm in total length. Our preliminary results show some significant similarities with the cardiac development of higher vertebrates, in spite of about 400 millions years of divergent evolution. The dogfish cardiac tube is composed of endocardium and myocardium separated by a thick layer of cardiac jelly. Large clefts form in the atrial and ventricular myocardium before the cardiac jelly disappears. These clefts seem to be related to the origin of the intertrabecular sinusoids. Myocardial pores in the sinus venosus and atrium might allow the flow of some cardiac jelly to the subepicardial space. Two atrioventricular and three conal endocardial cushions are formed by epithelial-mesenchymal transformation. The atrioventricular and conal valves seem to develop from these cushions, while the sinoatrial valve seems to derive from two transversal infoldings of the cardiac wall. The epicardium forms from mesothelial cells proceeding first from the liver and sinus venosus lining, and then from the developing septum transversum. A subepicardial space appears early and it is populated by mesenchymal cells which seem to proceed at least partly from the epicardium. These subepicardial cells apparently form capillary-like structures some of which coalesce in large annular veins around the atrioventricular and conoventricular grooves. The veins connect with ventricular sinusoids and the sinus venosus lumen.

We have recently reported that ischemia causes myocardial ammonia production which is not due to amino acid breakdown. The purpose of this study was to identify the remaining possible sources of ammonia production. The prospects were either deamination of AMP to inosine monophosphate (IMP), or adenosine to inosine. Eight intact extracorporally perfused pig hearts were rendered regionally ischemic by reducing the left anterior descending coronary artery blood flow by 60% for 40 minutes. Adjacent myocardium supplied by the circumflex artery was held aerobic throughout the study. Myocardial oxygen consumption and regional systolic shortening in the left anterior descending perfusion bed fell by 50 and 32%, respectively. Myocardial ammonia production increased significantly (p = 0.008) and tissue ammonia concentration was 55% greater in the ischemic left anterior descending bed than in the aerobic circumflex bed (p = 0.003). Compared to the circumflex bed, ATP and creatine phosphate concentrations in the left anterior descending bed were decreased by 41 and 53%, respectively. There were no significant increases in AMP or IMP levels, however there were dramatic increases of 525 and 397% in adenosine and inosine levels in the ischemic tissue. Thus, myocardial ammonia production was stimulated by ischemia without an increase in IMP levels. Combined with the fact that adenylate deaminase levels in the swine myocardium are normally low, this leads to the likely conclusion that source of the increased myocardial ammonia production during ischemia is deamination of adenosine, not IMP formation from AMP.

The size of the heart varies very little over a whole range of normal physiological activities. Physiologists, in animals and man, measure changes in cardiac output and heart volumes during exercise. Cardiac output can increase 5, 6, or 7 times in athletes but the stroke volume never more than doubles, the end-diastolic volume increases only by about 50% and the end-systolic (residual) volume decreases by the same amount; the heart rate increases about two and a half times in the untrained to 5 times in the physically fit athlete. It certainly appears as though there are some controlling mechanisms. The best way to consider these potential controlling mechanisms is not to accept the proposition that the heart provides most of the force necessary to propel the blood round the body during these various activities; this only occurs when you are flat on your back with your chest and abdomen open--not a very common occurrence. It is easier to regard the heart as having mechanisms available to it which allow the heart to accept all the blood which is pumped back to it during activity by the muscle pumps. The Frank-Starling mechanism allows an increased force of contraction to follow an increase in volume of each chamber, but from the evidence provided above this is by no means the whole story. It is proposed that changes in heart rate form the basis of the mechanism controlling the heart volumes and its size. Evidence is provided to allow me to postulate that the atrial receptors and the effect on blood volume and the effect on heart rate together form a remarkable control system which controls the size of the heart--and keeps it small.

Transcriptional regulatory mechanisms which mediate cardiac-specific gene expression have not yet been completely understood. Potential cardiac-specific promoter sequences, sharing similar protein binding motives, show either coexpression in skeletal muscle, local restriction to the atrium or late onset of expression during fetogenesis. Based on in situ hybridization studies that indicated the expression of the cardiac myosin-light-chain-2 (MLC-2) gene in ventricular myocardium and in the lower outflow tract, a model system for selective targeting of foreign genes to the heart of transgenic mice has been developed. The regulatory promoter element was derived from the rat cardiac MLC-2 gene. 2100 bp of the 5' regulatory MLC-2 sequences were found to drive constitutive cardiac expression of a firefly luciferase reporter gene from early tubular heart formation. During ventricular loop and septum formation luciferase activity was 10-fold upregulated in comparison to steady-state levels observed 10 days after birth. No luciferase activity was detectable in any other muscle or non-muscle tissue of transgenic mice. These data suggest that the 2.1 kb DNA sequences of the 5' flanking region of the cardiac MLC-2 gene contain sufficient regulatory elements for a selective gene expression in cardiac myocytes from embryogenesis. The transgenic model should aid in determining the influences of pathogenic gene products on developing and mature heart muscle to elucidate the etiology of myocardial diseases such as cardiomyopathies.