John C. Rose

Diverse Distribution of Red Cells and Albumin in the Dog Kidney

Cr31 labeled red cells and I131 human serum albumin were injected intravenously into 8 mongrel dogs. After 1 hour kidneys were removed and frozen rapidly with dry ice. Sections of outer cortex, inner cortex, outer medulla, inner medulla, outer papilla and inner papilla were removed and analyzed for Cr51 and I131 radioactivity. Tissue radioactivity was compared with that of arterial blood and concentrations of labeled red cells and albumin were calculated. No significant difference was found in relative red cell and albumin content between outer and inner cortex. The magnitude of the I131 albumin content in the cortex is interpreted to indicate a sizeable extnivascular exchangeable albumin pool. The renal papillae were extraordinarily deficient in red cells, but contained per 100 Gm., albumin equivalent to that of 39 ml. of plasma.

Vascular responses to arachidonic acid in the perfused canine lung.

We compared the effects of arachidonic acid (AA), the bisenoic prostaglandin precursor, with those of prostaglandin F2α (PGF2α) and norepinephrine (NE) on pulmonary vascular resistance in the isolated (in situ), perfused canine lung lobe. The isolated lobe was perfused with autologous blood or an artificial perfusate under conditions of constant flow. Lobar artery and venous pressures were constantly monitored after bolus injections of A A, PGF2α and NE into the inflow cannula. AA (100 μg/kg) produced a significant increase in the pressure gradient (93.3 ± 8.4%, se) in the lobe. Similarly, PGF2α (1 μg/kg) significantly increased the pressure gradient (41.2 ± 6.5%), as did NE (1 Mg/kg, 41.6 ± 3.2%). Aspirin (25 mg/kg) completely blocked the pulmonary vascular effect of AA, but did not affect the response to PGFfe, Linoleic acid, a control fatty acid, did not produce pulmonary vasoconstriction. The pressor effect of AA was not blocked by pretreatment with phentolamine, propranolol, cyproheptadine, or atropine. The use of an artificial perfusate free of cellular elements did not prevent the vasoconstrictor action of AA. The times to onset of action of the three agents were similar, and short. These results suggest that AA is converted into vasoactive intermediates or a prostaglandin, and the vasoactive intermediates or the prostaglandin act directly on precapillary pulmonary vascular smooth muscle rather than through platelet, plasma, adrenergic, or cholinergic mechanisms.

Effects of arachidonic acid on systemic arterial pressure, myocardial contractility and platelets in the dog.

Summary The bisenoic prostaglandin precursor, arachidonic acid (AA), in a single dose intravenously, produced a marked vasodepres-sor response in dogs, and a weak and variable effect on myocardial contractility. This response differed from the vasodepressor effect of PGE2 in that the onset of effect was delayed (15 sec for AA, 4.5 sec for PGE2) and PGE2 always caused a pronounced increase in myocardial contractility. Arachidonic acid caused thrombocytopenia and increased aggregability of platelets. All AA effects were inhibited by aspirin. The monoenoic prostaglandin precursor, dihomo-γ-linolenic acid, in doses equivalent to that of AA, had no effects. The data suggest that AA exerts its effects through conversion to an intermediate in the biosynthesis of PGE2 and not PGE2 itself. This work was supported, in part, by the Educational Foundation of America.

Cardiovascular and pulmonary effects of thromboxane B2 in the dog.

The hemodynamic properties of thromboxane B2(TxB2), a product of prostaglandin endoperoxide metabolism, have not been thoroughly described. TxBi is a bronchoconstrictor, but its effects on the systemic circulation and circulating platelets are unknown. Its precursor, thromboxane Ai (TxA,), is a potent vasoconstrictor as well as a platelet-aggregating agent Using intact anesthetized dogs, we investigated the effects of TxBj on pulmonary artery pressure (PAP), airway pressure (AP), systemic arterial pressure (SAP), and myocardial contractility (MC). Vascular responses were evaluated in relation to changes in platelet population and aggregability. Intravenous TxB2 (25 and SO pg/kg) increased AP (mean 62% and 69%) and PAP (50% and 86%), respectively, whereas SAP and MC responses were inconsistent. Left ventricular injections (25 fig/kg) also increased AP (36%) and PAP (36%). Intraventricular administration of TxBj produced a consistent elevation of SAP (10%) with a concomitant fall in MC (11%). These vascular responses were not consistent with alterations in platelet number or aggregability. A tachyphylactic response to TxB2, developed in AP and PAP at both dose levels and with both routes of administration. Intravenous and intraventricular TxB2, (26 pg/kg) produced a parallel decreasing response in PAP, suggesting the possible saturation of TxB2 binding sites or the depletion of a catabolic enzyme in the lung. Ore Res 44: 748-751, 1979

Antitussive activity of diphenhydramine in chronic cough

A double‐blind crossover study was conducted to evaluate the antitussive effectiveness of diphenhydramine (DPH) in chronic coughs related to bronchitis, at doses of25 and 50 mg every 4 hr for four doses. Both 25− and 50‐mg doses caused a statistically and clinically significant reduction in frequency of coughs, compared to placebo. The most frequently reported side effect was drowsiness, principally at the 50‐mg dose level. There was little or no apparent correlation between antitussive effectiveness and incidence of drowsiness, however, suggesting that the two effects were pharmacologically unrelated.

Cardiovascular Function in Hypothermic Anesthetized Man

Although hypothermia is being used as an adjunct to general anesthesia, its cardiovascular effects in man are not fully known. In this report the authors present the hemodynamic changes observed in patients undergoing hypothermia under the clinical conditions of its practical usage in the operating room. Considerable variability in vasomotor and cardiac responses was encountered, indicating that uniform behavior of patients to this agent is not to be expected in the relatively uncontrolled operating room setting; therefore, it should be used conservatively, particularly in critically ill patients in whom unexpected reactions may be disastrous.

Evidence for a Red Cell Shunting Mechanism in the Kidney

Simultaneous tagged red cell and tagged plasma albumin concentration-time curves were obtained from the renal vein without recirculation, following rapid injection of the indicators into a renal artery. The mean transit time of the red cells was consistently faster than that of the plasma albumin, but the washout downslopes of the indicators was found to be identical. This is interpreted as indicating that some red cells are shunted through those pathways of shortest length. The dynamic circulating hematocrit of the kidneys averaged 89 per cent of the large vessel hemato-crit. Intrarenal circulating blood volume averaged 24 ml./100 Gm. of dog kidney

Cardiovascular and Platelet Responses in the Dog to the Monoenoic Prostaglandin Precursor Dihomo-y-linolenic Acid

Summary The monoenoic prostaglandin precursor, dihomo-y-linolenic acid (DGLA), in a single dose intravenously (2.0 mg/kg) in dogs, produced a biphasic alteration in systemic arterial pressure (SAP) with a predominant and marked depressor effect. This SAP response is approximately equi-depressor to the effect of PGE1 5 μg/kg. DGLA had a positive inotropic effect, causing a greater increase in myocardial contractility than PGE1 in an equidepressor dose. The effect of DGLA on MC was not altered by ganglion blockade or β-adrenergic blockade. Aspirin blocked the sustained depressor response to DGLA but not an initial drop in SAP and increase of MC of very short duration. Aspirin had no effect on PGE1 or PGF1α responses. DGLA caused no thrombocytopenia, but caused a decrease in sensitivity to platelet aggregation. Control fatty acid injections produced variable effects with no resemblances to DGLA responses. It is concluded that DGLA produces direct depressor and positive inotropic responses as well as responses which may be due to conversion to an endo-peroxide formed in the biosynthesis of prostaglandins. In contrast, in equidepressor doses, arachidonic acid (AA), the bisenoic prostaglandin precursor, produces a delayed, single-phase depressor effect which may be due to endoperoxide formation alone. Further, the effect of AA on MC is reflex and is blocked by hexamethonium.

Cardiovascular responses to three prostaglandin endoperoxide analogs in the dog.

Summary Three stable analogs of prosta-glandin endoperoxides have been studied in limited quantities for their effects on the canine cardiovascular system. They are potent systemic pressor agents and powerful pulmonary vasoconstrictors. They directly increase myocardial contractile force. These responses are not altered by indomethacin. In their blood pressure and myocardial effects they are considerably more potent than arachidonic acid and may be estimated to be more potent than the primary bisenoic PGs, PGE2 and PGF20. The cyclic ether endo-peroxide analogs of Bundy are approximately twice as potent in their effects on these parameters as the azo analog of Corey et al.

The clinical measurement of retinal arterial pressure.

The determination of retinal diastolic arterial pressure by ophthalmodynamometry is described. In both normal and hypertensive subjects there was an average difference of 20 mm. Hg between retinal and brachial arterial diastolic pressures. The clinical usefulness of this procedure was demonstrated in patients with obstructive lesions in the internal carotid artery.