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Biomedical subjects

H R Kaplan

Publications and source records attributed to H R Kaplan.

53 records · Page 3Linked to original sources
PubMed1976

Sympathomimetic drugs: evaluation for acute central hypotensive activity in alpha-chloralose-anesthetized dogs and cats intravertebral artery administration,.

dl-Amphetamine, phentermine and their para-chloro derivatives were tested for acute central hypotensive activity after intra-vertebral artery (iva) infusions in alpha-chloralose-anesthetized cats and intact and carotid sinus denervated dogs. Iva clonidine (reference standard) caused immediate reductions in blood pressure and heart rate and carotid sinus denervation (CSD) enhanced the clonidine response. dl-Amphetamine and phentermine did not cause acute hypotensive responses in the dog or cat whereas their para-chloro derivatives did. The vasodepressor response to para-chloramphetamine was inconsistent and transient and not modified by CSD. The magnitude and duration of the chlorphentermine vasodepressor response was minimal in the intact and CSD dog compared to clonidine. In contrast, chlorphentermine in the cat (140-300 mug/kg) caused an acute hypotensive response comparable in magnitude to clonidine (0.6-1.0 mug/kg). The bradycardias observed after iva chlorphentermine were much less pronounced than those associated with iva clonidine at comparable vasodepressor doses. By the i.v. route, each drug caused only pressor responses in the dog and cat. Suppression of the pressor response (resulting from "spill-over" of these alpha-stimulants into the systemic circulation after iva dosing) in the dog with small doses of i.v. phenoxybenzamine did not unmask or enhance the vasodepressor or bradycardic actions to iva administration of drugs. Methysergide prevented the hypotensive response to chlorphentermine in the cat and partially suppressed the response to clonidine; the reverse was true after piperoxan. Lilly 110140 and para-chlorophenylalanine reduced or abolished the effects of iva chlorphentermine. In summary, (1) iva chlorphentermine and clonidine were the only alpha-sympathomimetics tested which were effective as hypotensive substances; (2) the cat was considerably more responsive to iva chlorphentermine than the intact or CSD dog; (3) iva clonidine was more bradycardic than iva chlorphentermine; and (4) both adrenergic and serotonergic components appear to be among the mechanisms involved in the acute iva hypotensive response to chlorphentermine in the cat.

Anesthesia↗
PubMed1975

Hemoglobin solution: a potential oxygen transporting plasma volume expander.

The potential of a 6% stroma-free human hemoglobin solution (WXb8326) as a plasma volume expander with oxygen transport capabilities was evaluated in barbiturate-anesthetized spontaneously breathing dogs. WXb8326 compared favorably with dextran-70 and 5% albumin solution as a plasma volume expander. Serial phlebotomies to a blood pressure of 35 mm Hg and immediate replacement with the above colloid expanders showed that only WXb8326-exchanged dogs survived acute reductions in hematocrit to critical levels of smaller than or equal to 5%. After several exchanges with WXb8326 to levels as low as 1%, it was possible to demonstrate acute survival. With less drastic reductions in the hematocrit (between 5 and 10%) all dogs survived acutely regardless of the type of plasma volume expander used; however, subacute survival rates varied. Oxygen transport characteristics during isovolumic hemodilution (phlebotomy and simultaneous replacement with WXb8326) were studied in a separate series of spontaneously breathing dogs in which hematocrit was reduced to approximately 50% of control. Oxygen content of erythrocytic hemoglobin (EHb) and extraerythrocytic hemoglobin (EEHb) resulting from infusions of WXb8326 was studied in arterial and venous blood at different levels of hemodilution. WXb8326 did not interfere with the arterial oxygen saturation of EHb in the pulmonary vascular bed and EEHb was oxygenated as efficiently as EHb. Oxygen delivery to tissues differed between EHb and EEHb. Erythrocytic hemoglobin met oxygen demands under basal conditions while EEHb contributed oxygen to tissues during conditions of high oxygen extraction. It is concluded that WXb8326 is an attractive condidate as a plasma volume expander with the capacity to transport oxygen to tissues.

Anemia↗
PubMedDate not supplied

Multiple molecular forms of phosphodiesterase and the regulation of cardiac muscle contractility.

Two approaches were taken to examine the role which the different forms of phosphodiesterase present in cardiac muscle play in regulating contractility. In an initial study, the effect of selective inhibitors of i) the calmodulin-stimulated phosphodiesterase (M & B 22, 948), ii) the cyclic GMP-stimulated phosphodiesterase (dipyridamole), and iii) the low Km, cyclic AMP-specific phosphodiesterase (imazodan) on the contractility of isolated guinea pig left atria was examined. Of the three selective phosphodiesterase inhibitors, only imazodan increased atrial contractility. In a subsequent study, the effect of imazodan on in vivo contractility was evaluated. Imazodan was found to potently increase contractility in the dog and the Rhesus monkey, while exerting only modest-to-minimal effects of contractility in the guinea pig and the hamster. Imazodan produced no positive inotropic effect in the rat. These species differences can apparently be attributed to i) the presence of subclasses of the low Km, cyclic AMP-specific phosphodiesterase (PDE III) in cardiac muscle, one of which is potently inhibited by the selective PDE III inhibitors imazodan, cyclic GMP and cilostamide, and the other which is selectively inhibited by rolipram and Ro 20-1724, and ii) variations in the intracellular localization of imazodan-sensitive subclass of PDE III. Thus, the maximum inotropic response to imazodan was observed only in those species in which the imazodan-sensitive subclass of PDE III was present and was membrane-bound, e.g., Rhesus monkey and dog. In the dog, the imazodan-insensitive subclass PDE III does not appear to play an important role in regulating cardiac contractility. These observations provide further support for the hypothesis that the inotropic response to imazodan, amrinone and related cardiotonics is due to their inhibitory effects on the cyclic AMP-specific form of phosphodiesterase, and also provides new insight into the relationship between cyclic AMP, phosphodiesterase and myocardial contractility.

3',5'-Cyclic-AMP Phosphodiesterases↗