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Biomedical subjects

J Holtz

Publications and source records attributed to J Holtz.

At least 145 records · Page 8Linked to original sources
PubMed1975

Effect of increased blood fluidity through hemodilution on general circulation at rest and during exercise in dogs.

During progressive normovolemic hemodilution with dextran-60, circulatory functions (cardiac output, oxygen delivery to tissues, arterial pressure and mixed venous oxygen saturation) and total body oxygen consumption were studied in conscious dogs at rest and during two levels of submaximal treadmill exercise. At rest, cardiac output rose continuously with progressive hemodilution. This increase, however, was not sufficient to compensate for the reduced arterial oxygen content. Consequently oxygen delivery fell significantly from 23.3 +/- 1.8 ml/min with kg at hematocrit 47.5% to 15.7 +/- 0.9 ml/min with kg at hematocrit 12.5%. The constant oxygen consumption was maintained by a simultaneous increase in oxygen extraction from blood. During the superimposed stress of exercise, a constant oxygen consumption was maintained between hematocrit ranges of 50 to 15 or 25%, respectively. Again, the increase of cardiac output due to hemodilution did not compensate for the reduced arterial oxygen content and consequently oxygen extraction rate was increased. These data demonstrate that at rest (and even more during submaximal treadmill exercise) the reduced whole blood viscosity or improved fluidity during hemodilution does not initiate an increase in cardiac output that is sufficient to maintain a constant oxygen delivery to the tissues.

Animals↗
PubMedDate not supplied

Apoptosis in the heart: when and why?

Since mammalian cardiac myocytes essentially rely on aerobic energy metabolism, it has been assumed that cardiocytes die in a catastrophic breakdown of cellular homeostasis (i.e. necrosis), if oxygen supply remains below a critical limit. Recent observations, however, indicate that a process of gene-directed cellular suicide (i.e. apoptosis) is activated in terminally differentiated cardiocytes of the adult mammalian heart by ischemia and reperfusion, and by cardiac overload as well. Apoptosis or programmed cell death is an actively regulated process of cellular self destruction, which requires energy and de novo gene expression, and which is directed by an inborn genetic program. The final result of this program is the fragmentation of nuclear DNA into typical 'nucleosomal ladders', while the functional integrity of the cell membrane and of other cellular organelles is still maintained. The critical step in this regulated apoptotic DNA fragmentation is the proteolytic inactivation of poly-[ADP-ribose]-polymerase (PARP) by a group of cysteine proteases with some structural homologies to interleukin-1 beta-converting enzyme (ICE-related proteases [IRPs] such as apopain, yama and others). PARP catalyzes the ADP-ribosylation of nuclear proteins at the sites of spontaneous DNA strand breaks and thereby facilitates the repair of this DNA damage. IRP-mediated destruction of PARP, the 'supervisor of the genome', can be induced by activation of membrane receptors (e.g. FAS or APOI) and other signals, and is inhibited by activation of 'anti-death genes' (e.g. bcl-2). Overload-triggered myocyte apoptosis appears to contribute to the transition to cardiac failure, which can be prevented by therapeutic hemodynamic unloading. In myocardial ischemia, the activation of the apoptotic program in cardiocytes does not exclude their final destiny to catastrophic necrosis with release of cytosolic enzymes, but might be considered as an adaptive process in hypoperfused ventricular zones, sacrificing some jeopardized myocytes to regulated apoptosis, which may be less arrhythmogenic than necrosis with the primary disturbance of membrane function.

Adult↗
PubMedDate not supplied

Transmural distribution of myocardial blood flow and of coronary reserve in canine left ventricular hypertrophy.

Left ventricular hypertrophy was induced by banding of the ascending aorta in pupies at the age of 6 weeks. At the age of one year left ventricular weight per body weight was increased by 87% compared to control litter mates. While myocardial perfusion and myocardial oxygen consumption per 100 g were identical in the hypertrophy and control group, there was a significantly diminshed ratio of subendocardial/subepicardial flow in the hypertrophy group during moderate exercise. With maximal coronary dilation subendocardial diastolic resistance (mm Hg/ml-min-1 per 100 g) was 0.16 +/- 0.03 in the control group and 0.26 +/- 0.03 in the hypertrophy group. This diminished coronary reserve indicates an insufficient growth of the vascular bed in these hypertrophied hearts.

Animals↗
PubMedDate not supplied

Hemodynamic and myocardial effects of long-lasting venodilation in the conscious dog: analysis of molsidomine in comparison with nitrates.

The effect of molsidomine-induced venodilation on cardiac preload was studied in conscious resting dogs, instrumented to analyze left ventricular function and myocardial perfusion. Direct effects on veins were studied during chloralose anesthesia by measuring regional venous capacitance changes with an induction angiometer. Kinetics of molsidomine-induced effects were compared to those induced by nitroglycerin and isosorbide dinitrate. This comparison was restricted to low i.v. dosages, causing only transient threshold effects on peripheral resistance and heart rate. During molsidomine-induced venous pooling, neither any direct effect on the coronary circulation nor any direct cardiac depressant activity of the drug was detected. 100 microgram/kg molsidomine caused a reduction of left ventricular preload by 5 mm Hg, lasting at least 4 hours. This effect was significantly more pronounced than that induced by 1 microgram/kg nitroglycerin or by 25 microgram/kg isosorbide dinitrate, lasting 2 min or 20 min, respectively. However, in raising regional venous capacitance, these nitrate dosages were equi-effective to 100 microgram/kg molsidomine, the effect of which was persistent and with a greater delay in onset. These results indicate that the lasting persistance of venodilation is a decisive factor for the amount of volume pooled in the capacitance system and, consequently, for the extent of preload reduction obtained. It is concluded, that lasting vasodilation, restricted to the veins, is beneficial for ventricular performance in ischemic heart disease.

Animals↗
PubMedDate not supplied

Transmural differences in myocardial blood flow and in coronary dilatory capacity in hemodiluted conscious dogs.

In 16 conscious resting dogs regional myocardial blood flow and the local coronary dilatory capacity were studied with the particle distribution technique during isovolemic hemodilution (hct = 13%). Postischemic peak coronary hyperemia following release of temporary circumflex coronary artery occlusion was used for quantification of regional coronary dilatory capacity. In hemodilution (arterial blood oxygen content less than one third of normal) left ventricular blood flow (LVBF) was 460 +/- 36 ml/100 g - min, subendocardial/subepicardial flow amounted to 1.3 +/- 0.1. During postischemic peak hyperemia LVBF increased by 33% up to 606 +/- 63 ml/100 g - min. This 33% increase in LVBF was distributed mainly to the subepicardial layer, while in the subendocardial layer there was no significant flow increase. It is concluded that the increase in heart rate and systolic coronary vascular compression in addition to the lowered arterial oxygen content lead to exhaustion of the dilatory reserve in the subendocardium during hemodilution. Therefore the remaining overall dilatory capacity is without functional significance.

Animals↗
PubMedDate not supplied

Ergonovine-induced constrictions of epicardial coronary arteries in conscious dogs: alpha-adrenoceptors are not involved.

The effect of i.v. ergonovine tartrate infusions (0.05-20 micrograms/kg/min, 12 minutes duration) on coronary arteries was studied in 14 conscious dogs instrumented to continuously measure vascular diameter by an ultrasonic dimension gauge using 10-MHz piezoelectric crystals. Ergonovine induced a biphasic coronary response: small, transient dilation during the first minutes of infusion, followed by slowly developing constriction reaching its maximum 5 to 15 minutes after the end of the infusion and persisting at this level for at least 10 minutes. The threshold dosage for significant constriction was 0.05 microgram/kg/min. A dosage of 5 micrograms/kg/min (cumulative 60 micrograms/kg, corresponding to 35 micrograms/kg ergonovine maleate) caused a decline in mean left circumflex artery diameter by 137 +/- 15 micrometers (= 4.6%) without significantly altering heart rate, plasma catecholamines or plasma renin activity. Coronary venous O2 saturation did not decline, indicating the absence of coronary resistance vessel constriction. The epicardial artery constriction was not attenuated by a vasopressin antagonist. Under adrenergic blockade (2 mg/kg phentolamine and 2 mg/kg nadolol) or under ganglionic blockade (5 mg/kg pentolinium tartrate), ergonovine (5 micrograms/kg /min) caused substantial elevation in mean arterial pressure, while the decline in coronary artery diameter was attenuated. When this increase in arterial pressure was prevented by appropriate bleeding, the ergonovine-induced coronary constriction was not diminished by adrenergic or ganglionic blockade. The serotonin antagonist methysergide (0.5 mg/kg) completely abolished the ergonovine-induced coronary artery vasomotion. It is concluded that ergonovine in dogs causes an epicardial coronary artery constriction comparable to the diffuse coronary artery narrowing in men not suffering from variant angina pectoris. These constrictions are not mediated by an adrenergic mechanism.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs.

The hemodynamic effects of the long-acting antianginal drug molsidomine were studied in 8 chronically instrumented conscious dogs by measuring the partition of the intravascular volume and the effective compliance of the total vascular bed. The blood volume of the resting dogs was varied by +/- 4 ml/kg in a cycle of blood infusion, withdrawal and reinfusion within 12 minutes. Relating the observed alterations in mean right atrial pressure to the induced changes in intravascular volume, an effective compliance of 2.9 +/- 0.4 ml. mm Hg-1 . kg -1 (mean +/- SD) was found. Heart rate, total peripheral vascular resistance and the local capacity of the distal femoral vein did not change significantly during the cycle of volume alterations. Following 0.1 mg/kg molsidomine i.v., mean right atrial pressure was lowered by 1.6 mm Hg and mean left atrial pressure by 3.4 mm Hg; the effective compliance was elevated to 4.7 +/- 0.6 ml . mm Hg-1. kg -1 (p less than 0.001), and the central blood volume was lowered from 17.8 +/- 3.1 to 14.8 +/0 3.3 ml/kg (p less than 0.01), while the total blood volume remained constant. The decline in stroke volume and the reflexly induced increase in heart rate correlated with the control heart rate. Mean arterial pressure declined from 101 +/- 7 to 91 +/- 14 mm Hg (p less than 0.05) and total peripheral vascular resistance remained unaffected. It is concluded that molsidomine exerts exerts its hypotensive effect by dilation within the vascular low-pressure system and that this dilation can be described quantitatively in conscious animals by the analysis of the total effective vascular compliance.

Animals↗