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Biomedical subjects

M D Thames

Publications and source records attributed to M D Thames.

At least 37 records · Page 2Linked to original sources
PubMed1992

Procainamide inhibits sympathetic nerve activity in rabbits.

Procainamide has been used extensively for the treatment of ventricular arrhythmias. It is widely held that the sympathetic nervous system plays an important role in the pathogenesis of ventricular arrhythmias. We investigated the possibility that procainamide has effects on the sympathetic nervous system by determining the responses to procainamide of postganglionic renal and preganglionic lumbar nerve activity in rabbits with sinoaortic and vagal denervation. Bolus administration of procainamide (3, 7, and 15 mg/kg) resulted in dose-dependent decreases in renal sympathetic nerve activity (26%, 38%, and 57%, respectively). These boluses resulted in plasma levels of procainamide of 13.3, 23.6, and 41.7 micrograms/ml, respectively. The same doses of procainamide resulted in decreases in lumbar nerve activity of 36%, 36%, and 41%, respectively. In a separate group of rabbits pretreated with hexamethonium (n = 8), 15 mg/kg procainamide reduced lumbar nerve traffic by 38%. Infusion of procainamide at 1 mg/kg/min over 20 minutes (n = 9) resulted in a decrease in renal sympathetic nerve activity of 20% with a plasma level of 11 micrograms/ml. Sham-treated rabbits (n = 8) exhibited an 18% increase in traffic over a comparable period of time. We conclude that procainamide inhibits lumbar and renal sympathetic nerve activity through effects on the brain or spinal cord. The influence of procainamide on sympathetic nerve activity may contribute importantly to its efficacy in the therapy of ventricular arrhythmias.

Animals↗
PubMed1991

Reflex control in heart failure: a primer for physicians.

Heart failure, cause notwithstanding, is characterized by adaptive (but harmful) increases in sympathetic activity and hormone levels, as well as by abnormal cardiovascular reflexes. Such reflex derangements may contribute to neurohumoral excitation. Consequently, normalization of the reflexes may be an important determinant of the effectiveness of therapy.

Adaptation, Physiological↗
PubMed1991

Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog.

BACKGROUND: Left ventricular sympathetic afferent nerves are located mainly in superficial epicardial layers. Reflex excitatory responses mediated by sympathetic afferent nerves have been observed during myocardial ischemia in cats and humans but not in dogs. Previous canine studies have induced ischemia by occlusion of a coronary artery. Extensive collateral circulation in the canine heart may limit ischemia of epicardial layers during simple coronary occlusion, resulting in little stimulation of sympathetic afferent nerves and minimal reflex excitatory responses. METHODS AND RESULTS: In anesthetized dogs with sinoaortic and vagal deafferentation, we determined whether reflex sympathoexcitatory responses mediated by sympathetic afferents occurred during transmural myocardial ischemia. Reflex sympathoexcitation was quantitated by direct recording from either efferent renal (n = 20) or cardiac (n = 5) sympathetic nerves. Responses of arterial pressure and efferent sympathetic nerve activity were measured during simple occlusion of the anterior descending artery (LAD alone) and during LAD occlusion with a circumflex stenosis (LAD + CIRC). This circumflex stenosis was adjusted to abolish coronary vasodilator reserve without reducing basal flow. We observed significantly greater reflex increases in renal (32 +/- 5%) and cardiac (58 +/- 15%) nerve activity during LAD + CIRC than during LAD alone (14 +/- 6% and 8 +/- 7%, respectively). Reflex changes in renal nerve activity during LAD + CIRC were abolished by interruption of cardiac sympathetic afferent pathways (n = 5). In eight experiments, myocardial blood flow was measured during the two coronary occlusions. These experiments confirmed that LAD + CIRC elicited more transmural ischemia in the LAD distribution than did LAD alone. However, these experiments also revealed that LAD + CIRC elicited endocardial ischemia in the circumflex distribution. In five additional experiments, regional sympathetic deafferentation of the posterior left ventricle by epicardial application of 88% phenol along the atrioventricular groove had no significant effect on renal nerve responses to LAD + CIRC (36 +/- 5% increase before phenol versus 31 +/- 3% increase after phenol). These results indicate that endocardial ischemia in the circumflex distribution did not contribute to the reflex increases in nerve activity that were noted during LAD + CIRC. CONCLUSIONS: Reflex sympathoexcitation mediated by cardiac sympathetic afferents can be elicited in dogs. However, these responses are significant only during ischemia that is transmural and involves the superficial epicardial layers of the left ventricle.

Afferent Pathways↗
PubMed1990

Subnormal parasympathetic activity after cardiac transplantation.

Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6.

Atrial Function↗
PubMed1990

Changes in regional adrenergic tone during sustained ventricular tachycardia associated with coronary artery disease or idiopathic dilated cardiomyopathy.

The hemodynamic tolerance of an episode of ventricular tachycardia (VT) can vary widely from no decrease in systolic blood pressure to severe hypotension. Little is known about the factors responsible for these different responses in man. Previous animal studies have suggested an important role for vasoconstriction mediated by the alpha-adrenergic nervous system. To determine the magnitude and time course of changes in alpha-adrenergic tone during symptomatic sustained monomorphic VT, VT cycle length, mean and phasic arterial pressure, forearm blood flow (by venous occlusion plethysmography) and forearm vascular resistance were measured in 15 patients. Nine of these patients were studied before and after regional intraarterial alpha blockade with phentolamine. After the induction of VT (350 +/- 68 ms), mean forearm blood flow decreased from 3.2 +/- 1.1 to 2.2 +/- 0.8 ml/min/100 ml (p = 0.0002) and the forearm vascular resistance increased from 32 +/- 14 to 40 +/- 14 units (p = 0.01). There were no significant differences for forearm vascular resistance during the first and last 30 seconds of VT (41.3 +/- 14 vs 37 +/- 13 units). After the infusion of intraarterial phentolamine, there were no significant changes in the VT cycle length or mean arterial pressure, but the forearm vascular resistance increase during VT was blunted by 60 to 70%. Most patients with symptomatic VT demonstrate sympathetic vasoconstriction and these changes are maximal during the first 30 seconds of VT. This sympathoexcitatory response is due largely to stimulation of alpha-adrenoreceptors and may be mediated by arterial baroreflexes.

Cardiomyopathy, Dilated↗
PubMed1990

New insights into pacemaker syndrome gained from hemodynamic, humoral and vascular responses during ventriculo-atrial pacing.

Ventricular pacing is performed during programmed electrical stimulation and during normal functioning of single chamber (VVI or VVIR) pacemakers. In many patients, retrograde ventriculoatrial (V-A) conduction may occur and evoke hemodynamic and reflex neurohumoral responses, which are unique to this pacing mode. Accordingly, forearm blood flow, forearm vascular resistance, mean and phasic arterial pressure, cardiac output and plasma norepinephrine, epinephrine and dopamine were measured during atrial, ventricular and V-A pacing at a cycle length of 600 ms (100 beats/min) before and after regional alpha blockade with intraarterial phentolamine in 16 patients with a left ventricular ejection fraction greater than 35% and little or no symptoms of congestive heart failure. During V-A pacing, cardiac output decreased by 10%, whereas forearm vascular resistance increased from 52 +/- 7 to 70 +/- 9 U (p less than 0.001) and plasma norepinephrine increased from 183 +/- 27 to 232 +/- 27 pg/ml (p less than 0.01). Phentolamine nearly abolished the increase in forearm vascular resistance in response to V-A pacing (18 +/- 4.1 U before vs 5.8 +/- 1.5 U after, p less than 0.05). The change in forearm vascular resistance with V-A pacing correlated with systolic arterial pressure, but not with changes in mean arterial pressure, pulse pressure, cardiac output, mean or peak right atrial pressure, pulmonary artery or pulmonary capillary wedge pressure. These results suggest that forearm vascular resistance responses to V-A pacing are mediated mainly by alpha-adrenergic receptors, through the arterial baroreflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

A simplified technique for the production of heart failure in the dog by rapid ventricular pacing.

Prolonged rapid ventricular pacing (VP) in dogs produces low output heart failure (HF) characterized by cardiomegaly, ascites, and elevated plasma renin and norepinephrine levels. Commercially available pacemaker generators have a protective circuit that prevents pacing at rapid rates. Previously, investigators have had to use either external temporary pacemakers or customized generators to pace at rates greater than 130 beats per minute (bpm). The authors have developed a simple method to perform rapid VP by gluing magnets on Medtronic VVI generators, which allows programming in a temporary mode to sustain rates up to 400 bpm. Our results using 10 generators in 55 dogs demonstrates that HF is produced in all dogs when VP is maintained at 250 bpm for an average of 28 days. Technical difficulties during our early experience with this technique included magnets becoming unglued, loss of capture, and wound complications requiring generator removal. Thus, our method reuses commercially available generators to rapidly pace the ventricles and induce HF.

Animals↗
PubMed1990

Effects of desipramine hydrochloride on peripheral sympathetic nerve activity.

Tricyclic antidepressants cause orthostatic hypotension and have antiarrhythmic effects that may be partially due to effects on the sympathetic nervous system. We studied the influence of intravenous desipramine hydrochloride on renal (n = 12) and lumbar (n = 5) nerve traffic and mean arterial pressure in alpha-chloralose-anesthetized rabbits with sinoaortic and vagal denervation. Desipramine administration resulted in dose-dependent inhibition of renal and lumbar nerve activity that was markedly reduced or abolished by yohimbine (0.5 mg/kg iv), an alpha 2-blocker that enters the brain rapidly. In contrast, administration of phentolamine (0.75 mg/kg iv), an alpha 1- and alpha 2-blocker with limited access to the brain, failed to alter the responses to desipramine. Because renal nerves are postganglionic and lumbar nerves are preganglionic, desipramine does not act via a ganglionic mechanism. Our results are best explained by an effect of desipramine on the sympathetic nervous system mediated via central alpha 2-receptors. This sympathoinhibitory effect of desipramine may contribute to its postural hypotensive effect and to its efficacy as an antiarrhythmic agent.

Adrenergic alpha-Antagonists↗
PubMed1990

Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity.

After cardiac transplantation, the denervated donor atria and ventricles demonstrate increased sensitivity to infusions of sympathomimetic amines. Recently, supersensitivity of the canine sinus and atrioventricular (AV) nodes to acetylcholine has also been demonstrated after parasympathetic denervation. Acetylcholine and the endogenous nucleoside adenosine exert similar electrophysiological effects in both the sinus and AV nodes, and share a common transduction process. We, therefore, hypothesized that after orthotopic cardiac transplantation, the donor (denervated) sinus node would demonstrate greater sensitivity to exogenous adenosine than the recipient (innervated) sinus node. The effects of incremental doses of intravenous adenosine (37-112 micrograms/kg) on changes in sinus cycle length (SCL) (delta SCLmax%), changes in PR interval (delta PRmax%), time to peak effect (sec), and duration of electrophysiological effects (sec) were prospectively measured in 28 orthotopic cardiac transplant patients and nine control subjects. The baseline SCL was 795 +/- 71 msec for the control subjects, 891 +/- 43 msec for the recipient atria, and 700 +/- 18 msec for the donor atria (p less than 0.05, donor vs. recipient). The delta SCLmax% for each dose of adenosine was similar in the innervated control and recipient atria. In contrast, the donor sinus node demonstrated a threefold to fourfold increased response to adenosine as compared with the recipient sinus node and a threefold to sixfold increased response as compared with control subjects. Similarly, the donor AV node demonstrated a threefold to fivefold increase in PR interval as compared with control subjects. The duration of sinus node slowing in the denervated atria was threefold to fivefold longer than in the recipient and control atria (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Crossover in baroreflex pathways controlling renal sympathetic nerve activity.

Experiments were performed to investigate the physiologic significance of the crossover of baroreceptor afferent input to the contralateral nucleus tractus solitarius (NTS) in terms of reflex control of renal sympathetic nerve activity and to determine the physiologic significance of neuronal crossover which may occur beyond the NTS. Experiments were done in 14 alpha-chloralose anesthetized rabbits. Baroreflex control of left renal nerve activity was determined from responses to phenylephrine-induced increases and nitroglycerin-induced decreases in arterial pressure. Under control conditions, the mean regression slope for changes in renal nerve activity (imp/sec/mmHg change in arterial pressure) was -2.2 +/- 0.5. After unilateral NTS lesion (n = 14) the gain of the reflex was -2.4 +/- 0.4 imp/sec/mmHg. Denervation of baroreceptors ipsilateral to the NTS lesion (n = 6) did not alter the regression slope (-2.7 +/- 0.5 imp/sec/mmHg), but interruption of the contralateral carotid and aortic baroreceptor afferent fibers (n = 8) markedly reduced the slope of the linear regression relationship from -2.4 +/- 0.3 to -1.1 +/- 0.3 imp/sec/mmHg. We interpret these data to suggest that baroreceptor afferent input exerts its major reflex influence via the ipsilateral NTS and that there is modest influence exerted by fibers which cross over to the contralateral side. In addition, since we recorded from the left renal nerves and alternated the side of the NTS lesion, we interpret our findings regarding a lesion in only one NTS to suggest that there is crossover in the baroreflex pathway beyond the NTS which permits the NTS on one side to exert an influence on the renal nerves on the contralateral side similar to that seen when the NTSs on both sides are intact.

Animals↗
PubMed1989

Neurohumoral and hemodynamic effects of lower body negative pressure in patients with congestive heart failure.

Baroreflex modulation of forearm vascular resistance (FVR) has been reported to be abnormal in patients with congestive heart failure (CHF). However, the neurohumoral mechanisms for this impairment are not defined. We assessed the responses of arterial pressure, FVR, plasma norepinephrine, and plasma renin activity to lower body negative pressure in 29 patients with compensated CHF (New York Heart Association class III and IV) and in 11 normal age-matched control subjects. Baseline mean arterial pressure (83 +/- 2 vs 84 +/- 2 mm Hg) and mean arterial pressure during LBNP (-10, -20, and -40 mm Hg) were not significantly different in the two groups. Basal FVR (43.7 +/- 4 vs 27 +/- 2 units), plasma norepinephrine (605 +/- 81 vs 155 +/- 8 pg/ml), and plasma renin activity (8.3 +/- 1.7 vs 1.2 +/- 0.2 ng/ml/hr) were significantly (p less than 0.01) higher in patients with CHF. The relative increases in FVR responses during LBNP of -10, -20, and -40 mm Hg (10 +/- 4% vs 70 +/- 12%, 17 +/- 6% vs 106 +/- 21%, and 24 +/- 9% vs 152 +/- 28%) were markedly attenuated in patients with CHF compared to control subjects. Plasma norepinephrine and plasma renin activity responses during LBNP were also attenuated in patients with heart failure. Our results suggest that baroreflex control of FVR and plasma norepinephrine and plasma renin activity is impaired in CHF because of the inability of the cardiopulmonary baroreceptors to alter sympathetic outflow.

Adult↗
PubMed1989

Subnormal heart period variability in heart failure: effect of cardiac transplantation.

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Adult↗
PubMed1989

Vagal cardiopulmonary baroreflex activation during phenylephrine infusion.

Phenylephrine infusion (PE) has been used to raise arterial pressure (BP) in order to investigate reflex responses mediated by sinoaortic baroreflexes (SAB). Increases in cardiac filling pressures have been reported during PE. Our experiments determined whether PE selectively activates SAB without activation of vagal cardiopulmonary baroreflexes (CPR). We measured changes in mean BP, mean pulmonary arterial pressure (PAP), and renal sympathetic nerve activity (RSNA) during PE in alpha-chloralose-anesthetized dogs before and after sinoaortic denervation (SAD; n = 10), selective vagotomy (n = 9), or SAD and vagotomy (n = 4). PE elevated both BP and PAP in all dogs studied. In dogs with SAB and CPR intact, RSNA was reflexively inhibited (% change RSNA: -76.3 +/- 4.7). In SAD dogs, inhibition of RSNA was significantly attenuated but not abolished (% change RSNA: -27.5 +/- 11.8). This inhibition after SAD correlated closely with increases in PAP. Small BP changes (10 mmHg) were associated with insignificant changes in PAP and RSNA. Volume expansion after SAD produced changes in PAP and RSNA similar to those produced by PE. After selective vagotomy, the sensitivity (% change RSNA/mmHg change BP) of the reflex elicited by PE was significantly decreased (-2.7 +/- 0.03 pre vs. -1.8 +/- 0.12 post; P = 0.01). PE failed to change RSNA after combined SAD and vagotomy. We conclude that vagal CPR contribute to reflex inhibition of RSNA during PE except when elevations of BP are small.

Animals↗
PubMed1989

Arterial baroreflex abnormalities in heart failure. Reversal after orthotopic cardiac transplantation.

Arterial baroreflex control of the heart and peripheral circulation is markedly impaired in humans and animals with congestive heart failure. After reversal of heart failure in animal models, arterial baroreflex control of heart rate remains impaired for up to 8 months. Cardiac transplantation restores normal ventricular function and completely reverses heart failure, but does it normalize arterial baroreflex control of heart rate in humans? We studied baroreflex sensitivity in 11 patients with severe heart failure, six normal control patients, and 23 patients at 2 weeks to 4 years after orthotopic cardiac transplantation. Baroreflex sensitivity was assessed with intravenous bolus injections of phenylephrine and is expressed as change in RR or PP interval (msec) per millimeters of mercury rise in systolic arterial pressure. Atrial rate of both donor (denervated) and recipient (innervated) atria were measured in the transplant group. Baroreflex sensitivity in patients with severe heart failure was 2.0 +/- 0.3 msec/mm Hg, but in patients after cardiac transplantation, it was 13.0 +/- 0.9 msec/mm Hg (p less than 0.001). The responses in the transplant group were similar to those observed in normal controls (10 +/- 1.2 msec/mm Hg, p = NS). Our data indicate that patients with severe congestive heart failure have marked abnormalities of baroreflex control, which are reversed as early as 2 weeks after cardiac transplantation. In view of this rapid reversal, we consider it unlikely that abnormal baroreflex sensitivity seen in heart failure is due to structural alterations in the baroreceptors. We speculate that neurohumoral rather than structural abnormalities account for depressed baroreflex sensitivity in heart failure.

Adult↗
PubMed1989

Effects of regional alpha- and beta-blockade on resting and hyperemic coronary blood flow in conscious, unstressed humans.

Our purpose was to determine if there are basal adrenergic influences on the coronary circulation in humans. We studied 56 patients with denervated hearts after cardiac transplantation and 19 normally innervated patients with angiographically normal coronary arteries. Coronary blood flow velocity was measured during cardiac catheterization with a subselective 3F intracoronary Doppler catheter. Heart rate was controlled by atrial pacing. Epicardial coronary artery diameter was measured by automated analysis of digital coronary angiograms. Coronary flow reserve was assessed by intracoronary papaverine hydrochloride (12 mg) injections. Regional sympathetic blockade was produced by intracoronary injections of phentolamine (3 mg, alpha) and propranolol (2 mg, beta) or metoprolol (3 mg, beta 1). After alpha-blockade, mean arterial pressure fell significantly (p less than 0.05) in both the denervated transplant (-5.8 +/- 1.5%) (mean +/- SEM) and normally innervated patients (-12.6 +/- 3.2%). Reductions in coronary flow velocity also were observed in these groups (-8.2 +/- 2.3% and -9.2 +/- 5.8%, respectively). Calculated coronary vascular resistance was unchanged. Similar changes were seen when patients were pretreated with beta-blockade before alpha-blockade. Nonspecific beta-blockade did not affect mean arterial pressure but decreased coronary velocity (innervated, -11.6 +/- 3.9%; denervated, -9.3 +/- 2.4%) and increased coronary vascular resistance (innervated, 15.4 +/- 6.7%; denervated, 10.2 +/- 3.7%). Coronary vascular resistance did not rise in either group after selective beta 1-blockade with metoprolol. Coronary flow reserve did not change in either patient group after either alpha- or beta-blockade. Changes in epicardial coronary artery diameter were small and generally not significant. These data suggest that alpha-receptor-mediated vascular tone is negligible in both denervated transplant patients and normally innervated patients. Additionally, the increase in vascular resistance after nonselective beta-blockade is the result of direct beta 2 vascular effects. Our data further suggest that there is little adrenergically mediated epicardial artery tone (either humoral or neural) at rest and that maximal vasodilator responses are not limited by adrenergically mediated vasomotor tone.

Adrenergic alpha-Antagonists↗
PubMed1989

Ventricular sensory endings mediate reflex bradycardia during coronary arteriography in humans.

It has been suggested that the response to the intracoronary injection of radiographic contrast is reflex in origin and results from stimulation of ventricular sensory endings. Cardiac transplantation results in denervation of the ventricles, and thus, may interrupt the afferent limb of this reflex. In contrast, the recipient sinus node and atrial remnant remain innervated, leaving the efferent cardiac limb of this reflex intact. We hypothesized that if contrast-induced reflex bradycardia and hypotension occurred from stimulation of ventricular chemosensitive endings, then this response would be abolished after cardiac transplantation. To test this hypothesis, we determined the changes in recipient (innervated) and donor (denervated) sinus-node rates (SNR) and mean arterial pressure during selective right (RCA) and left coronary artery (LCA) injection during arteriography in cardiac transplant patients and in patients with intact cardiac innervation. An increase in the recipient SNR was observed in cardiac transplant patients during left and right coronary injections (LCA, 6.6 +/- 1.7 beats/min; RCA, 2.4 +/- 1.4 beats/min) compared with a decrease in the control subjects (LCA, -15.3 +/- 2.3 beats/min; RCA, -6.9 +/- 1.9 beats/min; p less than 0.05 vs. control). This occurred despite significant and comparable decreases in mean arterial pressure in cardiac transplant patients (LCA, -12.7 +/- 2.3 mm Hg; RCA, -11.4 +/- 2.2 mm Hg) and control subjects (LCA, -18.7 +/- 1.7 mm Hg; RCA, -10.7 +/- 1.6 mm Hg). The donor SNR slowed for LCA injection (-5.4 +/- 2.1 beats/min, p less than 0.05) and RCA injection (-3.0 +/- 1.7 beats/min), which, for the LCA, was less than the slowing of control subjects (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1989

Reflex responses to myocardial ischemia and reperfusion. Role of prostaglandins.

Powerful vasodepressor and cardioinhibitory reflexes are activated in humans during inferior wall myocardial ischemia or infarction and during restoration of flow to the ischemic region. Experiments in dogs have demonstrated that these responses are due to stimulation of afferent vagal fibers that are located mainly in the inferior wall of the heart. Prostaglandins are released during myocardial ischemia and possibly during reperfusion. Prostaglandins stimulate chemosensitive but not mechanosensitive endings in the ventricles. Our studies determined whether blockade of prostaglandin synthesis with indomethacin or sodium meclofenamate decreased the reflex inhibitory responses to coronary occlusion and reperfusion. Experiments were done in alpha-chloralose-anesthetized dogs after sinoaortic baroreceptor denervation. Occlusion of the circumflex coronary artery for 5 minutes resulted in decreases in arterial pressure and in renal sympathetic nerve activity. During the first 5 minutes after release of the occlusion, renal nerve activity remained inhibited. After treatment with indomethacin (n = 6, 5 mg/kg i.v.) or sodium meclofenamate (n = 3, 4 mg/kg i.v.), coronary occlusion resulted in significantly less inhibition of renal nerve activity. Renal nerve activity returned to control during the first minute of reperfusion. In six additional experiments the responses to coronary occlusion and reperfusion were not altered by treatment with vehicle. Our data suggest that prostaglandins serve as the major stimulus to ventricular sensory endings during myocardial ischemia and reperfusion. Our data further suggest that reflex inhibitory responses during ischemia and reperfusion are due mainly to stimulation of chemosensitive endings.

Afferent Pathways↗