Efficacy of subarachnoid meperidine for labor analgesia.

Meperidine is an opioid agonist with known weak local anesthetic properties. To determine the efficacy of subarachnoid meperidine as a labor and delivery analgesic, 20 term parturients were given 10 mg meperidine via continuous spinal catheter. Visual analog pain scores on a ten-point scale and patient satisfaction scores on a four-point scale were measured before and after establishment of the block and one hour after maximum block was achieved. Time to pain relief and return of pain was recorded. Additional doses of 7 mg meperidine were given subarachnoid via the catheter when patients requested additional analgesia. Follow-up assessment 24 hours postpartum was used to determine overall patient satisfaction. Visual analog pain scale scores (mean +/- SD) were 8.57 +/- 1.43 before block, 0.62 +/- 0.89 immediately after block, and 0.33 +/- 0.57 at one hour after block (p less than 0.0001). Patient satisfaction scale scores (mean +/- SD) were 0.83 +/- 0.88 before block, 3.90 +/- 0.37 immediately after block, and 3.85 +/- 0.31 at one hour after block (p less than 0.0001). At follow-up, 14 of 18 patients rated satisfaction as excellent, with the remaining 4 rating it as good. Expulsive efforts were excellent in 14, good in 3, and fair in 1; 2 patients had cesarean sections. Mean time to onset of pain relief was 3.9 minutes (range, 2-12), with analgesia lasting a mean of 83 minutes (range, 38-180). Two patients developed slight motor block. Side effects appeared insidiously and are similar to those observed with other neuraxial opioids.

Frog ventricle: participation of SR in excitation-contraction coupling.

Activation of the first beat (B1) following a 60-s pause is diminished in isometrically contracting frog ventricular strips, in contrast to the augmentation documented for sarcoplasmic reticulum (SR)-dependent mammalian myocardium. However, treatment of frog ventricular strips with ouabain, an indirect inhibitor of the sarcolemmal Na+-Ca2+ exchanger, selectively enhanced postpause beats suggesting that in the absence of ouabain significant extrusion of cellular Ca2+ occurred during the pause. Because resting tension did not increase during the pause in ouabain-treated strips, the nonextruded Ca2+ must have been sequestered into a compartment such as SR. Steady-state beats were not affected by ouabain; its actions appeared to be separate from its known positive inotropism. Caffeine, a direct SR stimulus, initially enhanced B1 and subsequently decreased activation of all beats, which was consistent with initial augmentation of SR Ca2+ release and subsequent depletion of SR Ca2+ stores. Ouabain both potentiated the stimulatory effects and blocked the inhibitory effects of caffeine, suggesting that ouabain increased Ca2+ stores in the same intracellular Ca2+ pool as that acted on by caffeine, the SR. Ryanodine, an inhibitor of SR in mammalian myocardium, did not affect activation of frog myocardium. SR may be an important site for activator Ca2+ cycling in frog myocardium under control conditions as well as after long diastolic intervals in the presence of ouabain.

Myoglobin facilitated oxygen diffusion maintains mechanical function of mammalian cardiac muscle.

Myoglobin, an intracellular iron containing protein that binds oxygen reversibly, has been shown in model systems to facilitate the diffusion of oxygen and thereby maintain the mechanical function of exercising canine skeletal muscle and of hypoxic benthic fish hearts. Since no such role has yet been established for mammalian cardiac muscle small diameter (less than or equal to 0.70 mm) isolated kitten papillary muscles were stimulated at 24 X min-1 under isometric conditions in a physiological bath maintained at 30 degrees C with an oxygen tension of approximately equal to 450 mm Hg (59.8 kPa) to obtain a level of oxygenation just adequate to meet the metabolic needs of the muscles, as confirmed experimentally. Myoglobin was inactivated by adding 2 X 10(-3) mol X litre-1 sodium nitrite to the bath to abolish the facilitated diffusion of oxygen in the presence or absence of glycolytic blockade by 10(-4) mol X litre-1 sodium iodoacetate. This resulted in a 22(8)% (with blockade) or 10(3)% (without blockade) decrease (p less than 0.05) in the maximal rate of relaxation (-dT/dtmax) of the papillary muscles. Since the depression in mechanical function was reversible by increasing the bath oxygen tension to approximately equal to 600 mm Hg (79.8 kPa) it is concluded that the myoglobin facilitated diffusion of oxygen plays a role in maintaining the mechanical function of mammalian cardiac muscle under normal conditions. Furthermore, the maximal rate of relaxation of cardiac muscle is a sensitive indicator of the presence of hypoxia.

Reflex hypotension due to regional activation of left ventricular mechanoreceptors to explain the hypotension noted in clinical myocardial ischaemia or reperfusion.

To determine if regional increases in myocardial contractility, as may occur clinically in angina pectoris, myocardial infarction, or coronary thrombolysis, can initiate the reflex hypotension that sometimes accompanies these conditions, regional injections of positive inotropic agents were made into 32(3)% of the left ventricular myocardium in seven pneumonectomised dogs on total cardiac bypass. The coronary and systemic circulations were isolated and perfused separately. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in resistance. Regional injections of doses from 0.001 to 1.0 micrograms noradrenaline in a 0.1 ml volume appreciably increased regional contractility, detected visually and by strain gauge arches, whereas global contractility (left ventricular peak dP/dt) was increased much less. This caused a fall in the systemic pressure (resistance) of 14(2)% below the control value of 78(5)mm Hg, at the largest dose. The decreases in resistance were abolished by bilateral vagotomy, proving their reflex nature. The smaller (0.0001-0.01 micrograms) doses of noradrenaline and the smallest (0.25 micrograms) dose of veratridine increased regional contractility almost without increasing global contractility, indicating that the increase in regional contractility was the major cause of the reflex decrease in systemic resistance. In one animal a decrease in contractility in a control myocardial region occurred simultaneously with the experimentally produced increase in regional left ventricular contractility. This decrease may be analogous to the increase in contractility in the non-ischaemic left ventricular myocardium that occurs simultaneously with the decrease in contractility in the ischaemic region in clinical or experimental myocardial infarction. Left ventricular mechanoreceptors in the region with increased contractility probably initiate the reflex hypotension that sometimes occurs in both circumstances. Thus in angina pectoris or acute myocardial infarction the reflex hypotension probably originates in the hyperactive non-ischaemic myocardial region, whereas in coronary arterial thrombolysis it probably originates in the newly reperfused, formerly ischaemic, region.

Postoperative respiratory complications in non-idiopathic scoliosis.

The medical records of 303 patients undergoing fusions for scoliosis correction were retrospectively reviewed. The frequency and type of postoperative respiratory complications were compared in idiopathic versus non-idiopathic scoliosis patients in relation to age, type of spinal fusion procedure, pulmonary function test (PFT) results and preoperative diagnoses. The following factors were found to increase the incidence of problems in the postoperative period: a non-idiopathic type of scoliosis, mental retardation, anterior spinal fusion procedures, age of 20 or more years, a relative arterial hypoxemia and an obstructive component to the PFT's. Topics for further investigation are suggested.

Use of intracoronary KCl in the beating and asystolic heart to determine the mechanism of initiation of the left ventricular mechanoreceptor reflex.

To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkaloids, but with a negative inotropic effect, was studied in beating and verapamil-asystolic hearts. Five dogs were placed on a total cardiac bypass, pneumonectomised and their coronary and systemic circulations isolated and perfused separately, at a constant rate, so that changes in systemic pressure reflected changes in systemic resistance. Injection of 5 mmol X litre-1 KCl into the isolated coronary circulation caused cardiac asystole and a resultant reflex rise in systemic pressure (resistance) of 26 +/- 9% (p less than 0.05) above the control of 10.5 +/- 0.7 kPa (79 +/- 5 mmHg). This pressure rise, which indicates predominance of KCl's mechanical, negative inotropic over its chemical depolarising effect, was abolished by vagotomy, indicating its reflex nature. Contrariwise, in five other pneumonectomised dogs, similarly perfused on total cardiac bypass but with cardiac asystole from intracoronary verapamil, a subsequent, similar intracoronary dose of KCl now produced a fall in systemic pressure (resistance) of 8 +/- 2% (p less than 0.005) below the control of 12.8 +/- 0.5 kPa (96 +/- 4 mmHg). This pressure fall, presumably due to chemical depolarisation of the left ventricular mechanoreceptors, was also abolished by vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

A Ca2+-dependent mechanism for the positive inotropic response to an increase in afterload in cat papillary muscle.

In cat papillary muscles, under control conditions (1.25 mmol/L Ca2+ bathing solution, 25 degrees C), increasing the afterload by switching from isotonic to isometric contraction elicited a positive inotropic response. Halving the bath [Ca2+] resulted in a percentagewise similar or greater positive inotropic response to increased afterload, while doubling the bath [Ca2+] reduced and caffeine abolished or reversed this response, indicating [Ca2+]i predictably influences it. Since it was markedly reduced by verapamil and unaffected by propranolol, the positive inotropic response to increased afterload was concluded to be largely due to increased Ca2+ influx, unrelated to catecholamine release, caused by increased mean muscle length over time owing to the changing from isotonic to isometric contraction. While at 25 degrees C, increasing the afterload caused a positive inotropic response at 12 to 48 stimulations/min, at 37 degrees C and at similar frequencies, a negative inotropic response occurred. This reversed to a positive inotropic response at 86 stimulations/min, well below the normal cat heart rate, suggesting an increased afterload would cause a positive inotropic response via this mechanism in vivo, as observed for years in intact mammalian hearts. Similarities between positive inotropic responses to increased afterload in isolated cardiac muscle, isolated hearts, and intact animals indicate all may be examples of the same phenomenon (Anrep effect).

Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies.

Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs developed biventricular hypertrophy, four isolated left ventricular hypertrophy and four had no hypertrophy. The left ventricular systolic pressure was similar (P greater than 0.05) in these 3 banded groups (mean, 30 +/- 2 [SEM] kPa, [222 +/- 16 mmHg], n = 16). The left ventricle was divided into three coronal slices with approximately 59 samples being taken from subendocardial, midwall, and subepicardial layers and additional samples from the atria and right ventricle for regional myocardial flow measurement. As left ventricular hypertrophy increased, the subendocardial/subepicardial flow ratio decreased (r = -0.8). Heterogeneity of left ventricular regional myocardial flow, including a base-to-apex decrease in flow, present in controls, was markedly reduced in the banded dogs. Analysis of variance was found to be the most sensitive test for detecting left ventricular perfusion abnormalities since in banded dogs without hypertrophy, total and regional subendocardial/subepicardial flow ratios were not significantly different from control values, whereas the subendocardial circumferential flow pattern determined by analysis of variance was significantly different from control in these dogs (P less than 0.05).

The Bezold reflex: a special case of the left ventricular mechanoreceptor reflex.

Our previous finding that increasing myocardial contractility caused reflex systemic hypotension, the left ventricular (LV) mechanoreceptor reflex, suggested that the classical Bezold reflex (systemic hypotension and bradycardia after intracoronary administration of veratrum alkaloids) may be initiated by these same LV mechanoreceptors. In our working LV preparation with the coronary and systemic circulations isolated and perfused separately, intracoronary injection of veratrum alkaloids, like that of catecholamines or ouabain, had a positive inotropic effect which produced the hypotensive response typical of the LV mechanoreceptor reflex. To test directly if veratridine's positive inotropic effect initiates the Bezold reflex, verapamil, which blocks the slow Ca(2+) channels of myocardial cells but leaves intracardiac nerves unaffected, was injected by the intracoronary route to prevent the increased contractility from intracoronary injection of veratridine which also abolished the reflex hypotension, demonstrating conclusively that increasing myocardial contractility and thereby activating LV mechanoreceptors but not chemoreceptors initiates the Bezold reflex. Contrariwise, decreasing contractility or cardiac asystole by administration of tetrodotoxin, verapamil, or EDTA resulted in an increase in the systemic resistance, indicating that changes in the magnitude of the stimulus initiating the LV mechanoreceptor reflex (i.e., changes in myocardial contractility) lead to directionally opposite changes in peripheral resistance, as in the sino-aortic mechanoreflexes. Thus, it is concluded that the Bezold reflex is a special case of the LV mechanoreceptor reflex. The latter, by means of feedback mechanisms, functions normally by continuously matching the peripheral resistance to the LV contractile state so as to maintain the arterial pressure constant, thereby playing an important role in blood pressure regulation.

Recent developments in the measurement of cardiac output and regional blood flow using indocyanine green and microspheres.

Densitometric studies show that the large flow measurement errors and inability to obtain reproducible densitometer calibrations reported with indocyanine green (ICG) in nearly isotonic saline may have arisen from two sources: (a) slowed optical stabilization, and (b) sedimentation of dye aggregates formed in the salt "solutions" of ICG, both of which are avoidable by preparing the dye in water. The assumptions of the widely used regional blood flow measurement technique using radionuclide-labeled microspheres are described. Simultaneous injection of 8mu and 15mu microspheres in turkeys and in dogs demonstrated the existence of at least 8 mu arteriovenous communications (AVCs) in the stomach and intestine, not previously described by this technique, which, in addition to their physiologic functions, may play a role in production of acute gastric mucosal ischemia and erosions. Similar AVCs, producing a lesser degree of "shunting," were also found in the heart. Loss of 8 mu relative to 15 mu microspheres continued with time in the gastrointestinal circulation.

Simultaneous regional myocardial blood flows by tritiated water and microspheres.

Regional myocardial blood flow (RMF) was measured simultaneously by use of labeled 8-mum microspheres and the constant-rate infusion of 3H2O in 22 open-chest dogs (Na pentobarbital anesthesia) under markedly different hemodynamic conditions. Following cardiac excision, three adjacent 80-mg tissue samples were taken from the subendocardial, mid-wall, and subepicardial layers of quadrantal left ventricular (LV) segments of the basal and midventricular cardiac slices, and from one segment of the apical slice, totaling 81 samples per LV. RMF was calculated by the microsphere reference-flow technique and by two 3H2O tissue-uptake models. Good agreement between techniques (r=0.9-0.96) was found in comparing flows to the myocardial layers. Using Kety's "single-mixer" model of 3H2O tissue uptake, fairly good agreement was found between techniques in the 80-mg tissue samples; the cofficient of variation from regression was 18.5% which improved markedly to 12.3% when the flow values for each technique were averaged in the three adjacent samples. Analysis of variance showed that flow to the various LV subdivisions (layer, segment, slice) of control animals was heterogeneous.

Effect of nitroglycerin with and without systemic hypotension on canine regional myocardial tritiated water deposition.

A marked alteration in the transmural distribution of left ventricular blood flow, with a relative increase in subendocardial and mid-wall flows, but with no change in the distribution of the relative blood flow to the two ventricles occurred when nitroglycerin was administered and the systemic arterial blood pressure in the upper body maintained near control levels in anaesthetized, open-chested dogs. The relative increase in subendocardial and mid-wall flows may have resulted from a direct action of nitroglycerin on the coronary vasculature. On the other hand, the intravenous administration of nitroglycerin, when followed by the hypotension which it produces, did not alter the transmural distribution of blood flow in the left ventricle of the dog. Blood flow to the right ventricle relative to flow to the left ventricle increased in this situation.