Left Injection Research Articles

USE OF NICOTINE, BRADYKININ AND VERATRIDINE TO ELICIT CARDIOVASCULAR CHEMOREFLEXES IN UNANAESTHETIZED RABBITS

1. We have characterized in unanaesthetized rabbits the reflex effects of injecting nicotine into the pericardial sac or left atrium on heart rate, arterial pressure, systemic vascular resistance and the amplitude and frequency of respiration. These effects were compared with those of atrial administration of nicotine and veratridine, and intrapericardial administration of veratridine and bradykinin. 2. Injection of nicotine (6.25-400 micrograms) into the pericardial sac caused dose-dependent falls of heart rate and arterial pressure, and a brief period of hypopnoea. The fall in arterial pressure was mainly due to a fall in systemic vascular resistance. The threshold dose was 25 micrograms. Near maximal falls in heart rate (108 beats/min) and arterial pressure (47 mmHg) occurred at a dose of 200-400 micrograms. The latency between injection and the onset of bradycardia was 3.0 s. 3. The effects of intrapericardial nicotine on arterial pressure and respiration were antagonized in a dose-dependent fashion by intrapericardial mecamylamine (1-100 micrograms/kg) but were unaffected by intrapericardial hyoscine methylbromide (10 micrograms/kg) or vecuronium (1-10 micrograms/kg). The haemodynamic and respiratory effects were abolished by intrapericardial procaine. The haemodynamic effects were increased, though not significantly, by sino-aortic baroreceptor denervation. In decerebrate, artificially ventilated rabbits, bilateral cervical vagotomy converted the hypotensive and bradycardic response into a slowly developing tachycardia without change in arterial pressure. 4. Left atrial injection of nicotine (6.25-100 micrograms) caused bradycardia, a rise in arterial pressure, and prolonged hyperpnoea preceded by transient hypopnoea. After sino-aortic barodenervation it caused profound falls in heart rate and arterial pressure and transient hypopnoea, which were abolished by intrapericardial procaine. 5. Intrapericardial injection of veratridine (50-100 micrograms) had no consistent effect under control conditions. After sino-aortic barodenervation it caused falls in heart rate and arterial pressure which were abolished by intrapericardial procaine. Left atrial injection of veratridine caused highly variable haemodynamic effects. 6. Intrapericardial bradykinin (2.5-25 micrograms) caused rises in both arterial pressure and heart rate. These were abolished by intrapericardial procaine. 7. We conclude that when nicotine is injected into the pericardial sac of conscious rabbits the reflex haemodynamic and respiratory effects are due to the selective activation of neuronal-type nicotinic cholinoceptors on vagal afferents that originate in the epicardium. The reflex effects of left atrial nicotine are probably due to the excitation of a combination of carotid chemoreceptors and cardiac receptors. 8. The effects of nicotine, veratridine and bradykinin that we observed in conscious rabbits were profoundly different from those reported in anaesthetized rabbits.

Tracheal blood flow during spontaneous and mechanical ventilation of dry gases in sheep

Tracheal blood flow increases greater than twofold in response to eucapnic hyperventilation of dry gas in anesthetized sheep. To determine whether this occurs at normal minute ventilation, we studied sheep in which tracheal blood flow was measured in response to humid and dry gas ventilation while 1) awake and spontaneously breathing and 2) anesthetized and intubated during isocapnic mechanical ventilation. In additional sheep, three tracheal mucosal temperatures were measured during humid and dry gas mechanical ventilation to measure airway tissue cooling. Tracheal blood flow was determined by use of a left atrial injection of 15-microns-diam radiolabeled microspheres. Previously implanted flow probes on the pulmonary artery and the common bronchial artery allowed continuous recording of cardiac output and bronchial blood flow. Tracheal blood flow in awake spontaneously breathing sheep was 10.8 +/- 5.6 (SD) ml.min-1.100 g wet wt-1 while humid gas was breathed, and it was unchanged with dry gas. In contrast, isocapnic ventilation of intubated animals with dry gas resulted in a 10-fold increase in blood flow to the most proximal two-ring tracheal segment compared with that seen while humid gases were spontaneously ventilated [101 +/- 75 vs. 11 +/- 6 (SD) ml.min-1.100 g-1, P less than 0.05]. Despite a 10-fold increase in proximal tracheal blood flow, there was no response in distal tracheal and bronchial blood flow, as indicated by no change in the common bronchial artery blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent influence of left atrial pressure on regional peak lengthening rates

We examined the influence of left atrial pressure on regional peak lengthening rates in six open-chest dogs. Sonomicrometers were implanted in the midwall of the anterior apex, the midanterior wall, and the posterior wall of the left ventricle. A bolus of blood was injected into the left atrium during ventricular systole by a computer-driven power injector to produce an isolated increase in left atrial pressure without altering the peak rate of left ventricular pressure fall, regional systolic shortening, or end-systolic length. Several left atrial injections of different volumes were performed over a wide range of left ventricular end-diastolic pressure (LVEDP) (from 7 to 22 mmHg). The peak lengthening rate increased in direct proportion to the increase of left atrial pressure. This effect was significantly greater in the apical than midanterior or posterior sites and decreased at all sites at higher LVEDP. Similar size left atrial injections produced greater increases in atrioventricular pressure gradient but smaller increases in left atrial pressure at low compared with high LVEDP. We conclude that left atrial pressure is an independent determinant of regional peak lengthening rates in the intact left ventricle. The influence of left atrial pressure is attenuated at higher LVEDP because of a smaller change in the diastolic pressure gradient, although viscoelastic effects may play a role.

Coronary flow by left atrial and left ventricular microsphere injection in the rat

Previous studies have reported significantly higher variability in coronary blood flow (CBF) measurements obtained by microsphere injection into the left ventricle (LV) as compared with microsphere injection into the left atrium (LA) of the rat. Questions have arisen concerning whether or not some of the variability may have been due to successive rather than simultaneous injections at the two sites, thereby giving measurements at different cardiovascular states. To address this question, we measured cardiac output (CO) and CBF as well as other systemic organ blood flows by employing simultaneous injection of two different sets of radiolabeled microspheres into the left atrium and left ventricle of semiconscious rats. Using this technique, CBF values (ml.min-1.g-1) of 5.45 +/- 0.43 and 5.24 +/- 0.46 for LA and LV injection sites, respectively, were measured (all values reported as means +/- SE). CO values (ml/min) of 67.5 +/- 3.5 for LA and 67.6 +/- 3.4 for LV were obtained. Paired left atrial and left ventricular measurements of CBF, CO, and other systemic organ blood flows using tracer microsphere methodology were not significantly different. All variabilities in these measurements by LA and LV injection were not significantly different. Our procedure did not significantly alter physiological parameters such as heart rate, mean arterial pressure, hematocrit, or blood gases. These findings indicate that, in our rat model, measurements made by LV microsphere injection are not only adequate for determining systemic blood flow at distal beds but provide coronary blood flow data with variability not significantly different from that of left atrial injection.

Preferential proximal coronary dilation by activators of guanylate cyclase in awake dogs

The vasodilation effects of activators of guanylate cyclase, atrial natriuretic peptide (ANP), nitroglycerin (NTG), and acetylcholine (ACh), on the epicardial conductance arteries and the distal resistance coronary vessels were examined in chronically instrumented awake dogs and related serially to plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels. Left atrial bolus injections of ANP (3 micrograms/kg; n = 7), NTG (13 micrograms/kg; n = 7), or ACh (0.13 micrograms/kg; n = 3) induced sustained increases in epicardial coronary dimension (ultrasonic crystals), 3.3, 5.7, and 6.7%, respectively, lasting greater than 40 min for ANP and NTG and greater than 3 min for ACh, and relatively brief increases in blood flow (resistance artery vasomotion) for each agent. Plasma samples withdrawn serially after injections of each agent demonstrated that only ANP increased cGMP level; the time course of ANP-induced epicardial vasodilation followed more closely the increase in cGMP than that of plasma ANP. These data demonstrated that these three activators of guanylate cyclase induced preferential sustained epicardial vasodilation and only brief distal coronary vasodilation with minor or no change in systemic hemodynamics. The prolonged increase in plasma cGMP after ANP injection suggested continuous cGMP production during ANP-induced proximal vasodilation. These data demonstrate a striking heterogeneity of vasomotor responses in the coronary arterial vasculature and suggest that cGMP-mediated vasodilation mechanisms are more predominant in proximal conductance arteries compared with distal resistance vessels.

Differential modulation by pulmonary stretch afferents of some reflex cardioinhibitory responses in the cat.

1. Cats were anaesthetized with a mixture of chloralose and urethane, and were artificially ventilated, the thorax being opened via a medial sternotomy. 2. Various cardiovascular receptors were stimulated during reflex inhibition of the central inspiratory neurones produced by electrical stimulation of both superior laryngeal nerves simultaneously, while the afferent input from the lungs was held constant by temporarily interrupting artificial respiration, the lungs being held static in their expiratory position. 3. Reflex cardioinhibitory responses were elicited by stimulation of (a) the carotid body chemoreceptors by intracarotid injections of cyanide; (b) the arterial baroreflex by controlled elevations of the blood pressure; (c) the carotid sinus baroreceptors by raising the pressure in isolated perfused carotid sinus preparations; (d) cardiac receptors by left atrial injections of veratridine, and (e) pulmonary C fibres (including J receptors) by right atrial injections of phenyl biguanide. 4. The effects of single inflations of the lungs on these reflex cardioinhibitory responses were studied and compared with the effects of the various inputs alone. 5. Stepwise increases in lung volume, while having no consistent effect on arterial blood pressure, progressively diminished the arterial chemoreceptor-induced bradycardia to a value of about 7% of the control response without lung inflation. The pulmonary afferents were less effective on reflex responses from other inputs, the corresponding values being: arterial baroreflex, 66%; carotid baroreceptors, 66%, and cardiac receptors, 70%. These effects of lung inflation were abolished by selective denervation of the lungs. 6. In contrast, the size of the bradycardia evoked by pulmonary C fibre stimulation was, on average, unaffected by inflation of the lungs. In some tests the response was actually increased. 7. The differential modulation by lung inflation of these reflex cardioinhibitory responses were the same after upper thoracic sympathectomy indicating that pulmonary afferents and cardiac efferents involved fibres in the vagus nerves. 8. The possible central mechanisms responsible for the differential modulation by lung inflation of cardioinhibitory reflexes are discussed.

Alterations of coronary blood flow and reserve with aging in Fischer 344 rats.

To determine whether aging affects the coronary circulation, left and right ventricular coronary blood flow and vascular resistance at rest and after maximal vasodilation were measured by left atrial injection of radioactive microspheres in conscious, unrestrained male Fischer 344 rats at 4, 12, and 20 mo of age. As a function of age, maximal coronary blood flow per 100 g of tissue decreased by 43% in the left ventricle at both 12 and 20 mo, whereas a 44 and a 47% reduction was found in the right side of the heart at the same time intervals. Minimal coronary vascular resistance per 100 g of myocardium increased by 56 and 36% in the left ventricle and by 48 and 44% in the right at 12 and 20 mo, respectively. No change was found in total minimal coronary resistance for either ventricle despite an increase in myocardial mass. Maximal coronary blood flow per 100 g to the endocardium was depressed more than epicardial flow, leading to a 24% reduction in the endocardial-to-epicardial flow ratio at 20 mo. Coronary vascular reserve per 100 g, expressed as the increase in coronary blood flow during maximal coronary vasodilation, was greater in the right than in the left ventricle at all ages. It is concluded that the changes in coronary hemodynamics associated with maturation and aging are comparable with those seen in pressure overload hypertrophy with an increased vulnerability potential of the myocardium to ischemic episodes, particularly of the subendocardial region of the left ventricle.

Cardiovascular responses to stimulation of cardiac receptors in the cat and their modification by changes in respiration.

1. In cats anaesthetized with a mixture of chloralose and urethane, stimulation of cardiac receptors by left atrial injections of veratridine had little or no effect on pulmonary ventilation but caused bradycardia, systemic hypotension and hindlimb vasodilation with a latency of 3.3 s. 2. The hindlimb vasodilatation was due largely, if not entirely, to a reduction in sympathetic vasoconstrictor activity. 3. Similar cardiovascular responses occurred when the arterial blood pressure was maintained constant and also in artificially ventilated animals. 4. When the cardiac receptors were excited during a period of apnoea which was induced reflexly by electrical stimulation of the central cut end of a superior laryngeal nerve, the cardio-inhibitory response to left atrial injections of veratridine was enhanced but the size of the vasodilator response was unaffected. 5. In contrast, the cardiovascular effects of stimulation of the carotid body chemoreceptors, bradycardia and hindlimb vasoconstriction were enhanced by the laryngeal input. 6. The possible central mechanism responsible for the differential modulation of cardiac receptor and carotid chemoreceptor reflexes by respiration are discussed.

Measurement of bronchial blood flow with radioactive microspheres in awake sheep.

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of vagal and sympathetic afferents in reflex respiratory responses to capsaicin in dogs.

The respiratory responses following stimulation of type J (pulmonary C fiber) receptors by right atrial injections of capsaicin were assessed in spontaneously breathing anesthetized dogs. At the reflexly effective threshold dose, the primary respiratory response elicited was tachypnoea. With higher doses of capsaicin, the tachypnoea was replaced by apnoea. Left atrial injections of capsaicin also resulted in apnoea, which was abolished or reduced by injecting Xylocaine into the pericardial sac, and after vagotomy, apnoea was replaced by tachypnoea. The latter findings suggested that the apnoea produced by left atrial injection of capsaicin might be due to stimulation of receptors with vagal afferents coursing through the pericardium. In vagotomized dogs, administration of capsaicin into the abdominal aorta above the origin of the iliac arteries (the iliac arteries were kept occluded) resulted in a hyperpnoeic response. Following the transection of the spinal cord between L4 and L5, capsaicin injection into the abdominal aorta caused apnoea instead of hyperpnoea. The apnoeic response elicited was abolished by transecting the spinal cord between L1 and L2. It is suggested that the respiratory responses observed were due to stimulation of receptors in the splanchnic bed connected to sympathetic afferents.

Measurement of Regional

We measured blood flow within each of eight segments of the left ventricular myocardium in dogs by an Ultrafast CT scanner. The results were compared with flow determined by radiolabeled microspheres. Computed tomography (CT) flow was measured by an intravenous injection of nonionic contrast agent done simultaneously with the left atrial injection of microspheres. We calculated flow from the CT data by obtaining CT number versus time curves for regions of interest in the myocardium and by using a formula that related flow to both the time and value of the peak enhancement. Measurements were obtained in five dogs at rest and during hyperperfusion induced by chromonar. Based on 169 regional measurements, the Ultrafast CT and microsphere-determined flows correlated moderately (r = 0.68) over a range of 0.4 to 8 mL/min/g. However, when the data were divided into resting and hyperperfusion (ie, 20 to 30 minutes after the injection of the chromonar) states, a significant (P less than .001) increase in regional flow was determined from the CT measurements. The conclusion was that Ultrafast CT can distinguish between low and high myocardial flow states in dogs and has considerable potential for evaluating coronary flow reserve.

Lung reflexes and nasal vascular resistance in the anaesthetized dog.

1. In pentobarbitone-anaesthetized dogs the nasal vasculature was perfused on both sides, and nasal vascular and airflow resistances were measured together with blood pressure, heart rate and tidal airflow. 2. Capsaicin was injected intravenously to stimulate lung C-fibre receptors, and veratrine to stimulate pulmonary stretch receptors and cardiac receptors. Injections with both drugs were repeated after pulmonary denervation and after cervical vagosympathectomy. 3. Intravenous capsaicin caused hypotension, bradycardia and rapid shallow breathing, together with a decrease in nasal vascular resistance and little change in nasal airways resistance. Denervation showed that these effects came from lung reflexes, presumably from C-fibre receptors. 4. Intravenous veratrine caused similar effects to capsaicin before denervations, presumably due to stimulation of slowly adapting pulmonary stretch receptors. Left atrial injections of veratrine caused hypotension, bradycardia and hyperpnoea, together with an increase in nasal vascular resistance and little change in nasal airways resistance. Thus cardiac receptors seem to increase nasal vascular resistance. 5. Injections of capsaicin and veratrine into the nasal circulation decreased nasal vascular resistance, with a stimulation of breathing and changes in blood pressure. Denervations indicated that these were a combination of local and reflex actions.

Microsphere reference flow samples during systemic flow adjustment.

Regional myocardial blood flow measurements in the right heart bypass preparation can be particularly valuable, since this preparation provides control of the main hemodynamic determinants of coronary blood flow. We examined the validity of aortic reference flow samples in relation to coronary samples during continuous systemic flow adjustment for aortic pressure control in six dogs on right heart bypass, anesthetized with chloralose and urethan. Microsphere concentrations were compared in paired reference flow samples drawn from the aortic arch and from a coronary artery for 119 left atrial microsphere injections. During left subclavian artery infusion and during femoral artery infusion at rates above 2,000 ml/min, there were high percentage errors in microsphere concentration between paired samples, consistent with aortic sample dilution by systemically infused blood. In 52 injections during withdrawal or femoral infusion below 2,000 ml/min, at cardiac outputs of 390-4,800 ml/min, the percentage error was 0.001 +/- 1.18% (SE); the absolute value of this error was below 20% in 96%, and below 10% in 77% of these injections. Linear regression related these coronary to aortic microsphere concentrations by the equation Y = 1.005X - 1.64, r = 0.997, Sy.x = 13.2 (5.9%). (Sy.x represents the standard deviation from regression.) These data indicate that valid aortic reference flow samples can be obtained within specific hemodynamic conditions during systemic flow adjustment in the right heart bypass preparation.

The vasodilator effect of coronary vascular endothelium in situ: Its inactivation by hydroquinone

Studies were carried out to demonstrate the presence of the endothelium derived relaxing factor (EDRF) in coronary arteries in situ and the effect of hydroquinone on this factor. The studies revealed the presence of EDRF in coronary arteries of rabbit hearts remaining in situ. EDRF was inactivated by left atrial injection of hydroquinone. In situ constriction of coronary arteries by vasopressin was markedly increased following exposure to hydroquinone, and the dilatory response to acetylcholine was absent. The experiments confirm the presence of the endothelium derived relaxing factor in coronary arteries in situ and its inactivation by hydroquinone.

Relationship between CO and transit times for dye and thermal indicators in central circulation.

We investigated two factors that may influence the estimation of lung water by the thermal-dye double-indicator-dilution method: 1) changes in cardiac output (CO), and 2) thermal equilibration with cardiac tissue. In theory, the difference between mean transit times of thermal and dye indicators (delta MTT) is proportional to the extravascular volume of distribution of the thermal indicator (VODev) and inversely related to CO. The delta MTT also includes a time element DT due to the difference in response times of the measuring instruments such that delta MTT = VODev/CO + DT. In nine anesthetized dogs we recorded 286 aortic thermal and dye curves following left atrial (LA) and right atrial (RA) injections as CO was increased from 2.35 to 6.65 ml X s-1 X kg-1 by isoproterenol infusion, and a regression of delta MTT on CO-1 was performed. DT was measured in vitro for comparison with the y-intercept. In six of nine dogs the slope of the regression for LA injections was not different from zero, indicating that there is no measurable volume of distribution for thermal indicator in cardiac tissue. For RA injections the relationship between delta MTT and CO-1 was linear in all experiments, with an average correlation coefficient of 0.97 +/- 0.01 (SE), indicating that the VODev was constant over a threefold increase in CO. Although the in vitro measurement of DT agreed closely with the average of the y-intercepts of the regressions, small between-subject differences in DT can lead to apparent flow-related changes in extravascular thermal volume computed in the conventional fashion using the in vitro estimate of DT.

Stimulation of pulmonary C fibres decreases coronary arterial resistance in dogs.

A constant-flow preparation was used to assess coronary arterial resistance while activating pulmonary C fibres in chloralose-anaesthetized dogs. A Gregg cannula was passed through the left common carotid artery until the tip fitted snugly in the left circumflex coronary artery. The cannula was perfused with blood from the left femoral artery and blood flow through the cannula was maintained constant with a perfusion pump. Perfusion pressure in the coronary artery was measured from a side arm in the cannula, and resistance in that vessel was calculated as the ratio of pressure to blood flow. Capsaicin (10-20 micrograms/kg), injected into the right jugular vein, produced significant (P less than 0.05) decreases in heart rate, systemic arterial pressure, coronary arterial pressure and coronary arterial resistance. These responses were abolished by bilateral vagotomy. Neither left atrial injections of capsaicin nor acutely decreasing the systemic arterial pressure by occluding the inferior vena cava had a significant effect on the coronary arterial pressure or resistance. Additionally, overdrive pacing of the heart had no effect on the reflex decreases in coronary arterial pressure and resistance that were evoked when capsaicin was injected into the jugular vein. alpha-Adrenergic blockade reduced the reflex decrease in coronary arterial pressure and resistance evoked by capsaicin by 31 and 38%, respectively. Combined alpha-adrenergic and cholinergic blockade reduced the reflex decreases in both coronary arterial pressure and resistance by approximately 89%. These results indicate that activation of pulmonary C fibres produces a reflex decrease in coronary arterial resistance, and that this response is due to the combined effects of increased parasympathetic cholinergic activity and withdrawal of alpha-adrenergic tone.

Right ventricular coronary flow in arterial hypertension

Right ventricular (RV) coronary circulation in systemic hypertension offers an opportunity to assess the effects of marked increases in coronary perfusion pressure in vivo without appreciable increases in workload or marked hypertrophy of the cardiac chamber. This study investigates RV coronary circulation in renal hypertensive rats (RHR). Mean arterial pressure rose by 50% to 60% in RHR as compared to control groups and RV mass increased by 15% (7.15 vs 6.19 mg/gm body weight, p < 0.01). Coronary blood flow, which was measured by left atrial injection of microspheres in conscious rats, was not signficantly different between study groups both at rest and after maximal coronary vasodilation with carbochrome (6 mg/kg). However, minimal RV coronary resistance level per gram were significantly elevated ( p < 0.05) in RHR. A second study was designed to further dissociate the effects of arterial hypertension from the effects of changes in RV mass in RHR. In one group, blood pressure was acutely reduced by 1 week of captopril therapy, while RV mass remained high. In the second group, captopril was discontinued after 14 weeks of treatment, allowing arterial pressure to rise, while RV mass, which had regressed with treatment, remained normal. After treatment, RV minimal coronary resistance levels remained high in the short-term-treated hypertensive rats, but returned to normal levels in the long-term-treated RHR. These results suggest the following possibilities: (1) the RV is not immune to the effects of systemic hypertension, (2) coronary structural changes are probably the main factor that accounts for the increase in RV coronary resistance levels, and (3) coronary alterations are amenable to long-term antihypertensive therapy.

Pulmonary C-fibers reflexly increase secretion by tracheal submucosal glands in dogs

Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10-20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.

Effects of nisoldipine, a new calcium antagonist, on myocardial infarct size and cardiac dynamics following acute myocardial infarction.

While some calcium antagonists are effective in reducing myocardial infarct size, this beneficial effect may be accompanied by negative inotropic effects. In the following study, a new dihydropyridine calcium antagonist, nisoldipine, was assessed for its effect on infarct size, hemodynamics, and regional function as assessed by percent systolic wall thickening of the left ventricle (SWT) by 2D echocardiography. Open-chest, anesthetized dogs were subjected to 6 h of coronary artery occlusion. After 10 min of coronary artery occlusion, the ischemic area at risk of infarction (AR; % of left ventricle) was determined by left atrial injection of 99mTc-labeled albumin microspheres with subsequent postmortem autoradiography. After 6 h, the hearts were excised, and the area of necrosis (AN) determined by incubation of left ventricular slices in triphenyltetrazolium chloride stain. Treated dogs received 0.005 mg/kg nisoldipine by intravenous infusion at 1.91 ml/min (lasting approximately 8.7 min) during three dosing periods: 15 min, 2 h, and 4 h postocclusion. The AR of eight controls (25.7 +/- 1.8%) was not significantly different from that of 11 treated dogs (25.1 +/- 1.9%). However, the AN/AR X 100 of treated dogs was significantly less than that of controls (62.8 +/- 9.3 vs. 91.6 +/- 7.0%; p less than 0.05). Mean arterial pressure fell in treated dogs by 15.7% (p less than 0.01) at 15 min and by 5.7% (p less than 0.05) at 4 h but not at 2 h postocclusion. Heart rate was not affected by nisoldipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)