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Biomedical subjects

R C Koehler

Publications and source records attributed to R C Koehler.

151 records · Page 9Linked to original sources
PubMed1977

Influence of arterial hypoxia on cardiac and coronary dynamics in the conscious sinoaortic-denervated dog.

Arterial hypoxia was produced in 10 conscious, chronically instrumented, tracheostomized dogs by allowing them to breathe 7.5% O2 in N2 for 10 min. Hypoxia (Pao2 = 28 +/- 0.7 (SE) Torr) caused significant increases in coronary blood flow (+196%), left ventricular dP/dt max (+60%), aortic blood flow (+48%), heart rate (+50%), and left ventricular systolic (+12%) and aortic (+10%) pressures. Left ventricular end-diastolic pressure and stroke volume were unchanged, while systemic (-30%) and coronary diastolic (-66%) vascular resistances declined significantly. When equivalent levels of arterial hypoxia were produced in four of these dogs after chronic sinoaortic denervation, the coronary, cardiac, and systemic hemodynamic responses were not significantly different, with the exception that the small arterial pressure response was abolished. Thus the peripheral chemoreflexes are not essential for the normal coronary vasodilator and cardiac adjustments to occur during hypoxia in the conscious dog. The data support the hypothesis that a large part of the cardiac adjustments to hypoxia is initiated outside the sinoaortic reflexogenic zones, probably within the central nervous system.

Animals↗
PubMed1976

Heart rate and rhythm and intracranial pressure.

Cardiac slowing during elevated intracranial pressure (ICP) could be due to direct activation of central nervous system (CNS) centers or it may be secondary to baroreceptor reflexes activated by the associated pressor response. In five pentobarbital-anesthetized dogs when ICP was raised to 50 mmHg the heart rate decreased 34.4 beats/min (+/-4.8 SE). This cardiac slowing occurred when ICP was elevated after sinoaortic denervation (-24 +/- 4.43 beats/min) and also during elevated ICP when changes in arterial pressure were prevented (-32.3 +/- 4.25 beats/min). These results indicate that the cardiac slowing is largely of CNS origin. In dogs given morphine with pentobarbital to achieve slower heart rates, raising ICP to 50 mmHg by left-sided intracranial balloon inflation led to cardiac dysrhythmias in 9 of 12 dogs. By contrast, raising ICP to 50 mmHg by right-sided intracranial balloon inflation only produced progressive sinus bradycardia. These responses were related to a combined enhancement of vagal and sympathetic activity. Differences observed between right- and left-sides balloon inflation may be partly related to asymmetrical engagement of the cardiac autonomic nerves. The results suggest that left-sided intracranial lesions are more likely to produce cardiac dysrhythmias.

Animals↗
PubMedDate not supplied

An analysis of hypoxia in sheep brain using a mathematical model.

Cerebral blood flow (CBF) increases as arterial oxygen content falls with hypoxic (low PO2), anemic (low hemoglobin) and carbon monoxide (CO) (high carboxyhemoglobin) hypoxia. Despite a higher arterial PO2, CO hypoxia provokes a greater increase in CBF than hypoxic hypoxia. We analyzed published data using a compartmental mathematical model to test the hypothesis that differences in PO2 in tissue, or a closely related vascular compartment, account for the greater response to CO hypoxia. Calculations showed that tissue, but not arteriolar, PO2 was lower in CO hypoxia because of the increased oxyhemoglobin affinity with CO hypoxia. Analysis of studies in which oxyhemoglobin affinity was changed independently of CO supports the conclusion that changes in tissue PO2 (or closely related capillary or venular PO2) are predictive of alterations in CBF. We then sought to determine the role of tissue PO2 in anemic hypoxia, with no change in arterial and little, if any, change in venous PO2. Calculations predict a small fall in tissue PO2 as hematocrit decreases from 55% to 20%. However, calculations show that changes in blood viscosity can account for the increase in CBF in anemic hypoxia over this range of hematocrits.

Algorithms↗
PubMedDate not supplied

Sustained endothelial dependent dilation in pial arterioles after crosslinked hemoglobin transfusion.

Hemoglobin is known to bind nitric oxide (NO) with high affinity. Plasma-based hemoglobin may provide a more effective sink for NO than red cell-based hemoglobin because of a closer and consistent proximity to the endothelium. Despite the known endothelial tight junctions that exist in cerebral vessels, plasma-based hemoglobin may inhibit NO-derived vasoreactive mechanisms in brain. If so, the response to endothelial and non-endothelial dependent vasodilator substances should be affected. In pentobarbital anesthetized cats, we tested this hypothesis by measuring the pial arteriole blood vessel diameter using aa cranial window before and after systemic transfusion of a human crosslinked hemoglobin compound. We than topically applied solutions of endothelial dependent or endothelial independent vasodilators and an NO synthase inhibitor to the surface of the brain within the window and remeasured the arteriole size. Topical acetylcholine (Ach) increased diameter in all arteriole sizes. The corresponding increases in diameter to Ach in time control eats (32% hematocrit) and in albumin transfused cats (18% hematocrit) were similar to those in hemoglobin transfused cats. Likewise, size-dependent dilation to SIN-1 in the hemoglobin group was similar to that in the control and albumin groups. The pial arteriole response to adenosine diphosphate (ADP) and sodium nitroprusside (SNP) also increased arteriole diameter in small, medium and large arterioles. Superfusion with L-nitroarginine to inhibit NO synthase markedly reduced the dilator response to Ach and ADP but not to SIN-1 or SNP. Thus, prior crosslinked hemoglobin transfusion does not interfere with vasodilator responses to either Ach, ADP, SIN-1 or SNP. When dilute solutions of crosslinked hemoglobin were superfused abluminally in the cranial window in anesthetized but non-transfused animals, the dilator response to Ach was unchanged at 10(-4)M hemoglobin, was attenuated at 10(-7) and 10(-6)M hemoglobin, and was completely blocked at 10(-5)M hemoglobin. This finding implies negligible permeation of the blood-brain barrier by crosslinked hemoglobin acutely after the transfusion.

Acetylcholine↗