Leroy J. Hirsch

Hemodilution with oxyhemoglobin. Mechanism of oxygen delivery and its superaugmentation with a nitric oxide donor (sodium nitroprusside).

BackgroundHemodilution (HD) with oxyhemoglobin colloid (oxyHb) provides a greater arterial oxygen content (Cao2) than HD with conventional colloids; however, oxygen delivery (DO2) is essentially the same, because, in contrast to conventional HD, cardiac output (CO) is not augmented. This study seeks to elucidate the mechanism that limits CO during oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor would augment DO2, because oxyHb is known to inactivate in vitro endothelial-derived NO. MethodsAnesthetized dogs were isovolemically hemodiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO inactivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was titrated intravenously until decreases (>10 mmHg) in mean aortic pressure (Pao) indicated the presence of exogenous NO. Systemic hemodynamics and regional blood flows (microsphere method) were measured. ResultsAlbumin-HD and metHb-HD produced typical HD-mediated responses: increased CO (63–65%), slight decreases (13–15%) in DO2, decreases in systemic vascular resistance (SVR) proportional to the decreases (49–52%) in blood viscosity of all three groups, and increased regional blood flows (RBF). Responses to oxyHb-HD were atypical: CO and its determinants were not changed, DO2 decreased (23%) proportional to CaO2, and SVR and most RBF were not changed except for a net redistribution of CO to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2–5

Separation of Myocardial Versus Peripheral Effects of Calcium Administration in Normocalcemic and Hypocalcemic States Using Pressure-Volume (Conductance) Relationships

mUg. kg−1. min−1) induced comparable decreases in mean Pao (29–37%) and SVR (39–41%); however, CO, RBF, and DO2 were not affected. In oxyHb-HD, exceptionally large doses of SNP (54 ± 5

Effects of Fentanyl on Coronary Blood Flow Distribution and Myocardial Oxygen Consumption in the Dog

mUg. kg−1. min−1) decreased mean Pao only 19 ± 1%; however, CO increased 78 ± 5% and decreases (61 ± 3%) in SVR were slightly greater than viscosity reductions. Other determinants of CO were not affected. Most RBF increased proportional to CO; there was, however, preferential distribution to myocardium and skeletal muscle. Consequently, the augmented CO, and CaO2 of oxyHb-HD, produced large increases in DO2, 77 ± 5% from HD alone and 43 ± 3% from prehemodilution values. ConclusionsThis study indicates that the limited CO and DO2 of oxyHb-HD resulted from opposing changes in two determinants of flow, i.e., reduced blood viscosity and increased arterial resistance (vasoconstriction). The vasoconstriction was not evident with metHb-HD and was reversed by the SNP infusion, indicating that oxyHb inactivated in vivo endothelial-derived NO. The ability of the NO donor (SNP) to facilitate large viscosity-mediated increases in DO2 during oxyHb-HD is an important finding that could potentially render oxyHb colloids more useful than conventional colloids, particularly for the individual with a compromised circulation who would benefit from an increased oxygen supply.

Skeletal muscle blood flow and O2 uptake during intravenous nicotine with and without hypertension.

This study used left ventricular pressure-volume (conductance) relationships to separate the effects of calcium administration on myocardial performance and peripheral vasoconstriction in normocalcemic and hypocalcemic states. Hypocalcemia was produced in anesthetized dogs with intravenous citrate-phosphate-dextrose until serum [Ca2+] was approximately 0.7 mmol/L. Calcium (CaCl2) bolus (5 mg/kg) was administered during normocalcemia (n = 6) and hypocalcemia (n = 6), and data were collected at 1, 5 and 10 min after CaCl2 administration. During normocalcemia, CaCl2 administration increased [Ca2+] 19% at 1 min and was accompanied by a 47% (P < 0.05) decrease in left ventricular contractility (i.e., end-systolic elastance or E(lves)) and a 13% (P < 0.05) increase in systemic vascular resistance. At 5 and 10 min, serum [Ca2+] and the hemodynamic variables began to return to the baseline values. During hypocalcemia, E(lves) decreased 25% (P < 0.05), but after CaCl2 bolus, it increased to baseline levels and remained there during the 10-min period. Hypocalcemia and the CaCl2 bolus did not significantly affect SVR. In conclusion, these studies suggest that the indications for the use of calcium should depend on the initial serum level of ionized calcium.

Comparison of hemodynamic responses to pipecuronium and doxacurium in patients undergoing valvular surgery while anesthetized with fentanyl

Little data exist on the effects of fentanyl on coronary blood flow (CBF), myocardial oxygen balance, and the regional distribution of blood flow. These studies were designed to determine whether fentanyl had any intrinsic effects on myocardial oxygen consumption (MVO2) and blood flow distribution. In anesthetized dogs, fentanyl was administered in a dose of 50 micrograms/kg and various measurements were made at 5 and 20 minutes. After hemodynamic recovery from the fentanyl, the animals were treated with atropine to block the known vagomimetic effect of fentanyl and challenged with acetylcholine (3.5 micrograms/kg); then fentanyl (50 micrograms/kg) was again administered and measurements made at 5 and 20 minutes. In the untreated dogs at 5 minutes post-fentanyl, heart rate (HR) decreased 30% and at 20 minutes decreased 29%. Treatment with atropine essentially eliminated HR changes at both time periods. Mean arterial pressure (MAP) fell by 20% and 22% at 5 minutes and 20 minutes, respectively, in the untreated group, but when atropine was administered, MAP was observed to be intermediate between baseline and the untreated animals. Left ventricular MVO2 at 5 minutes in the untreated group was modestly but not significantly reduced. However, at 20 minutes post-fentanyl, MVO2 decreased significantly. MVO2 was essentially unchanged after atropine. Regional CBF (measured by radiolabelled microspheres) was unchanged at 5 minutes, but all layers exhibited significant reductions at 20 minutes. In the atropine group, only the LV epicardial area appeared to show decreases in flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine and phenylephrine effects on right ventricular function in experimental canine pulmonary embolism.

Summary: The mechanism by which nicotine causes peripheral vasoconstriction and its relationship to the increased risk of peripheral vascular disease in smokers are unknown. To study the peripheral vascular effects of nicotine, we measured hemodynamic responses and oxygen consumption of the in situ gracilis muscle during intravenous (i.v.) nicotine infusions in anesthetized dogs. Nicotine 36.0 μg/kg/min increased gracilis artery pressure (Pga) 91 × 17% and muscle vascular resistance (MVR) 96 × 18%. whereas muscle blood flow (MBF) and oxygen consumption (MVO2) were unchanged from baseline. In dogs with extracorporeal-controlled normotension during nicotine infusion, however. Pga was held at baseline levels but similar increases in MVR were observed (95 × 11%) as flows decreased 52 × 9%. Oxygen consumption decreased in direct proportion (53 × 5%) to MBF, indicating complete impairment of oxygen extraction (AVO2). Thus impaired oxygen extraction was masked in dogs in which Pga was allowed to increase because of sustained pressure-dependent flows. Phenoxybenzamine block of muscle α-adrenoceptors increased MBF and MVO2 in both normotensive and hypertensive dogs. Combined α- and β-blockade effectively neutralized all sympathoadrenal responses in the muscle. All the above results occurred regardless of innervation. Plasma levels of norepinephrine (NE) and epinephrine (EP1) increased <1,000% during nicotine infusion. Apparently, these levels were high enough to (a) override dilator effects of plasma EPI and (b) cause vasoconstriction in muscle independent of nerve supply. Infusion of nicotine in the gracilis artery had no effect on muscle hemodynamics. Nicotine-induced increase in plasma catecholamines resulted in a powerful constriction of both resistance and oxygen-exchange vessels of skeletal muscle. Our data suggest that elevated plasma catecholamines cause the increase in peripheral vascular resistance during nicotine intake and that blood flow and oxygen consumption are impaired in skeletal muscle, which is particularly evident in the absence of hypertension. These studies may have bearing on the pathophysiology of peripheral vascular disease in smokers who have elevated plasma catecholamines but who are not hypertensive.

Urine Hydrogen Peroxide During Adult Respiratory Distress Syndrome in Patients With and Without Sepsis

Hemodynamic responses to pipecuronium bromide or doxacurium chloride were compared in patients undergoing valvular heart surgery. Thirty ASA class III-IV patients of either sex, mean age 62 +/- 3 years (+/- SD), weight 70 +/- 3 kg, were randomly selected to receive either doxacurium (0.08 mg/kg) or pipecuronium (0.15 mg/kg). Hemodynamic parameters were determined at preinduction, induction, 2 minutes and 6 minutes following administration of the muscle relaxant. Anesthetic induction consisted of midazolam, 0.10 mg/kg, followed by fentanyl, 5 micrograms/kg. Measured or calculated parameters were as follows: mean arterial pressure, heart rate, cardiac index, mean pulmonary artery pressure, systemic vascular resistance index, central venous pressure, pulmonary capillary wedge pressure, stroke volume index, left and right stroke work indices, and pulmonary vascular resistance index. Awake patients who had been randomly assigned to the pipecuronium group had significantly higher pulmonary capillary wedge pressures (22 +/- 2 v 15 +/- 2 mmHg; P < 0.05) and heart rates (86 +/- 3 v 64 +/- 5 beats/min; P < 0.05) than awake patients in the doxacurium group. Following induction, both wedge pressure and heart rate were not significantly different between the two groups. Compared to hemodynamics at induction, there were no clinically significant changes following administration of pipecuronium or doxacurium.