Effects of endotoxin on coronary vascular resistance in the isolated blood-perfused rabbit heart

Rabbit hearts were excised and perfused with blood pumped through a cannula placed in the aortic root. A fluid-filled balloon-tipped catheter was positioned in the left ventricle for the measurement of left ventricular pressure and dP/dt. Total coronary vascular resistance (CVR) was calculated by dividing the coronary perfusion pressure by the rate of coronary blood flow. Following stabilization, coronary blood flow was held at a constant rate. Compared to control hearts, endotoxin (E. coli) added directly to the blood perfusate (6 mg/80 ml of circulating blood) had no effect on CVR or left ventricular dP/dt. In contrast, changing the perfusate to blood obtained from rabbits previously given endotoxin (LD100; 6 mg/kg IV) resulted in significantly higher CVR, without depression of left ventricular dP/dt. This increase in CVR was observed not only when the endotoxemic donor rabbits were hypotensive at the time the blood was obtained (4-6 hours following endotoxin administration), but also when the endotoxemic donors remained normotensive (blood withdrawn 30 minutes following endotoxin administration). A pathologic increase in CVR might contribute to the myocardial ischemia and contractile dysfunction observed in endotoxin shock.     

Exercise radionuclide ventriculography in children: normal values for exercise variables and right and left ventricular function.

Thirty two children (aged 5-19 years) with no clinical evidence of significant cardiovascular disease undertook continuous staged supine exercise on a bicycle ergometer. Multigated radionuclide ventriculography was performed at rest and during each exercise stage. Exercise duration and total workload both increased with age. Aerobic work correlated better with age than did total work. In most children the ejection fraction for both ventricles increased by at least 5% with exercise. Right ventricular ejection fraction did not decrease with exercise in any subject but left ventricular ejection fraction decreased by 2% and 9% in two. The response of end diastolic volume to exercise was variable, but there was a consistent decrease in mean (SD) end systolic volume of the left (29(22)%) and right (30(19)%) ventricles. Cardiac index (mean (SD)) increased by 234(65)% with exercise. The left ventricular:right ventricular end diastolic volume ratio (mean (SD)) at rest was 1.26(0.26). It is concluded that exercise radionuclide ventriculography is an excellent technique for a combined assessment of exercise capacity and an evaluation of ventricular size and performance in children. These values for supine bicycle exercise in children without significant cardiovascular disease will be useful for future comparisons with other groups.     

Cellular basis for age-related differences in cardiac excitation-contraction coupling

Clinical experience indicates that infants and young children respond to a variety of cardiovascular pharmacological and physiological interventions differently than adults. What is less clear, however, are the cellular and molecular mechanisms that contribute to these age-related differences. Based largely upon results from animal models, it is apparent that developmental changes occur in numerous pathways and proteins involved in the regulation of contractile function and in the determinants of inotropic responsiveness. The purposes of this review are to provide a brief overview of cardiac excitation-contraction and to illustrate some of the important age-related differences in the mechanisms involved in calcium regulation in the heart. This scientific foundation may help to explain certain clinical observations in the very young. Furthermore, it is hoped that a better understanding of the fundamental processes involved in controlling cardiac contractile function will stimulate additional research in the search for more specific, rational and age-appropriate cardiovascular therapeutics.     

18p- syndrome and hypopituitarism.

A patient is described with 18p- syndrome and hypopituitarism. This is the first patient with this syndrome who has been shown to benefit from growth hormone therapy. Patients with this syndrome who have growth deficiency should be considered for evaluation for hypopituitarism, if the quality of their lives would improve with an increase in stature.     

Developmental expression of NCS-1 (frequenin), a regulator of Kv4 K+ channels,in mouse heart

The channel proteins responsible for the cardiac transient outward K+ current (Ito) of human and rodent heart are composed, in part, of pore-forming Kv4.3 or Kv4.2 principal subunits. Recent reports implicate K+ channel interacting proteins (members of the neuronal Ca2+-binding protein family) as subunits of the Ito channel complex. We reported that another Ca2+-binding protein, frequenin [or neuronal calcium center protein-1 (NCS-1)], also functions as a Kv4 auxiliary subunit in the brain. By examining cardiac expression of NCS-1, the aim of this study was to examine the potential physiologic relevance of this protein as an additional regulator of cardiac Ito. Immunoblot analysis demonstrates NCS-1 protein to be expressed in adult mouse ventricle at levels comparable to that found in some brain regions. Cardiac NCS-1 protein expression levels are much higher in fetal and neonatal mouse hearts when compared with the adult. Immunocytochemical analysis of isolated neonatal mouse ventricular myocytes demonstrates co-localization of NCS-1 and Kv4.2 proteins at the sarcolemma. Given its high levels of expression in the heart, NCS-1 should be considered an important potential Kv4 regulatory subunit, particularly in the immature heart.     

Termination of sustained ventricular tachycardia by external noninvasive pacing

Cardiac pacing has proven useful in the termination of sustained ventricular tachycardia (VT). In this study, the effectiveness of external noninvasive temporary pacing was compared with traditional endocardial burst ventricular pacing for the termination of sustained and hemodynamically stable VT. In 14 patients, 16 VT morphologies induced by programmed right ventricular extrastimulation were reproducibly terminated by endocardial burst pacing (3 to 9 complexes). VT cycle lengths averaged 392 +/- 97 ms (standard deviation) and ranged from 300 to 690 ms. The endocardial burst pacing cycle length used to terminate VT averaged 298 +/- 93 ms (range 220 to 600 ms). External burst pacing terminated 14 of 16 VT morphologies (88%). The pacing cycle length used to terminate these 14 VTs averaged 282 +/- 44 ms. The number of ventricular captures ranged from 5 to 20 beats. Failure to terminate 2 VT morphologies probably represented a failure of the device to capture the ventricle. Acceleration of VT occurred in 1 patient with burst external noninvasive pacing. These observations suggest that external burst pacing may be an effective means of terminating sustained VT in some patients.     

Effects of postnatal maturation on postrest potentiation in isolated rabbit atria

Ultrastructural changes in cardiac sarcoplasmic reticulum (SR) have been reported during postnatal development of the mammalian heart, but the functional significance of these observations has not been well characterized. Calcium release from SR in intact myocardial preparations was determined by the contractile characteristics of postrest contractions. Isometric tension and the maximum rate of tension development of the first contraction following intervals of electromechanical quiescence (rest) were related to steady-state tension and maximum rate of tension development during contraction at constant frequency (1.0 Hz) in isolated left atrial strips from newborn (1-7 days), immature (14-21 days), and adult (more than 6 months) rabbits. The first postrest contraction was increased as a function of the rest interval rate of tension development, defined as postrest potentiation, in all three age groups and reached a maximum value at rest intervals of more than 20 s. Tension developed by the first contraction following a 60-s rest interval was potentiated less in newborn and immature atria than in adult atria at an extracellular calcium concentration ([Ca]e) of 2.5 mM, an age-related difference most marked in the immature. Ryanodine (5.0 X 10(-9) M), a putative blocker of calcium release from cardiac SR, abolished postrest potentiation providing evidence that calcium release from SR is the predominant determinant of the postrest contraction. Postrest tension in atria from the immature rabbit heart was significantly increased both in absolute terms and relative to steady-state tension following stabilization under conditions which increase intracellular [Ca] [( Ca]i), i.e. increasing [Ca]e, increasing tonicity, or decreasing extracellular sodium concentration ([Na]e).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the temporal profiles of vasopressin and oxytocin in the cerebrospinal fluid of the cat, monkey and rat

The temporal profiles of oxytocin were examined in the cerebrospinal fluid (CSF) of the cat and rat. Unlike the marked daily rhythm of oxytocin concentrations recently described in the CSF of the rhesus monkey, no daily rhythm of the peptide was evident in the CSF of either the cat or rat. The apparent species specificity of the CSF oxytocin profiles among these mammals is contrasted with the consistent expression of a daily rhythm of arginine-vasopressin in the CSF of each of the three species.