PubMed Health⌕ Search

Biomedical subjects

P B Adamson

Publications and source records attributed to P B Adamson.

At least 19 recordsLinked to original sources
PubMed1995

Do increases in markers of vagal activity imply protection from sudden death? The case of scopolamine.

BACKGROUND: Low-dose scopolamine increases heart rate variability (HRV) in patients with a prior myocardial infarction (MI). This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low-dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective. METHODS AND RESULTS: Nineteen mongrel dogs that survived an anterior MI were used in the study. Occurrence or lack of ventricular fibrillation (VF) due to acute myocardial ischemia during submaximal exercise identified dogs at high and low risk for sudden death. Dose-response curves performed in 12 dogs at high (n = 6) and low (n = 6) risk showed that scopolamine at 3 micrograms/kg exerts the greatest effect on HRV. A second group of 7 high-risk dogs were exposed to an exercise-and-ischemia test after treatment with scopolamine (3 micrograms/kg i.v.). Scopolamine increased the standard deviation of RR intervals by 41%, increased the high-frequency band of spectral analysis by 48%, and decreased resting heart rate by 14%. Despite the increase in markers of vagal activity, VF recurred during the exercise-and-ischemia test in 6 dogs (86%). CONCLUSIONS: The significant increase in HRV induced by acute scopolamine did not result in a decreased risk for VF due to acute myocardial ischemia in association with sympathetic activation. Caution must be applied when extrapolating the potential antifibrillatory activity of an intervention from its influence on autonomic markers.

Animals↗
PubMed1995

Heart rate variability during specific sleep stages. A comparison of healthy subjects with patients after myocardial infarction.

BACKGROUND: Heart rate variability (HRV) is typically higher during nighttime. This evidence supports the concept that overall, sleep is a condition during which vagal activity is dominant. Myocardial infarction (MI) results in a loss in the overall nocturnal HRV increase. However, the characteristics of HRV during specific sleep stages in normal subjects and, more importantly, after MI, are unknown. This study describes HRV during sleep stages in normal subjects and in patients with a recent MI. METHODS AND RESULTS: HRV was measured from 5 minutes of continuous ECG recording in 8 subjects with no clinical evidence of coronary artery disease (age, 47 +/- 4 years) and in 8 patients with a recent MI (age, 51 +/- 2 years; NS versus control subjects) in the awake state, non-rapid eye movement (REM), and REM sleep. In normal subjects, the low- to high-frequency ratio (LF/HF) derived from power spectral analysis of HRV decreased significantly from the awake state to non-REM sleep (from 4 +/- 1.4 to 1.22 +/- 0.33, P < .01). During REM sleep, the LF/HF increased to 3 +/- 0.74 (P < .01 versus non-REM, NS versus awake). In post-MI patients, the LF/HF showed an opposite trend toward an increase from 2.4 +/- 0.7 to 5.11 +/- 1.4 (NS, P < .01 versus the control subjects). REM sleep produced a further increase in the LF/HF up to 8.9 +/- 1.6 (P < .01 versus awake and versus REM in control subjects). CONCLUSIONS: Myocardial infarction causes a loss in the capability of the vagus to physiologically activate during sleep. This results in a condition of relative sympathetic dominance even in a situation such as sleep, normally described as a condition of vagal dominance and, consequently, low risk for lethal events. The evidence that the sleep-related vagal activation is lost after MI may provide new insights to understanding the nocturnal occurrence of sudden death.

Electrocardiography↗
PubMed1995

K+ channel blockade in the prevention of ventricular fibrillation in dogs with acute ischemia and enhanced sympathetic activity.

The value of K+ channel blockade in preventing lethal arrhythmias, and specifically those triggered by acute myocardial ischemia and sympathetic hyperactivity, remains unproven. To address this issue, we tested the antifibrillatory effect of d-sotalol, and Ikr blocker, d,l-sotalol, its racemic compound which blocks Ikr, and beta-adrenoreceptors, and propranolol. Ten dogs with a healed anterior myocardial infarction (MI) had ventricular fibrillation (VF) during a 2-min occlusion of the circumflex coronary artery performed toward the end of a submaximal exercise stress test. In successive trials in the same animals, d-sotalol (three injections of 8 mg/kg, one every 12 h), d,l-sotalol (8 mg/kg), and propranolol (1 mg/kg) were tested. All three interventions significantly reduced heart rate (HR) response to exercise, but only d,l-sotalol and propranolol also blunted the reflex HR increase during acute myocardial ischemia. With d-sotalol, HR at 30 s of coronary occlusion was similar (253 +/- 28 beats/min) to that observed in the control tests (259 +/- 35 beats/min). d-Sotalol prevented recurrence of VF in only 1 of 10 dogs tested. One dog was lost to the continuation of the study after occurrence of VF with d-sotalol. Six of 9 dogs (67%) tested with d,l-sotalol and 5 (56%) of the same 9 dogs tested with propranolol were protected from VF. d-Sotalol does not reduce risk of VF during acute myocardial ischemia associated with sympathetic hyperactivity, and lethal events can be prevented by antiadrenergic interventions.

Animals↗
PubMed1994

Baroreflex sensitivity: methods, mechanisms, and prognostic value.

A large bulk of data collected over the last 25 years links reflex autonomic activation during acute myocardial ischemia with risk of developing lethal arrhythmias. Specifically, evidence obtained in an experimental preparation in chronically infarcted dogs supported the concept that sympathetic hyperactivity enhances likelihood for ventricular tachyarrhythmias, vagal activation exerts protective effects. Based on this knowledge, it was first proposed by our group that analysis of autonomic control of heart rate could provide information relevant to risk stratification in post-myocardial infarction individuals. Among several possibilities, baroreflex sensitivity was evaluated by correlating blood pressure rise induced by bolus injections of phenylephrine with the consequent beat to beat R-R interval lengthening. Experimental studies involving direct recordings from single neural vagal fibers directed to the heart documented that baroreflex sensitivity closely reproduces cardiac vagal activity. In a large group of conscious dogs it was shown that a depressed baroreflex sensitivity was highly predictive of the risk for ventricular, fibrillation during acute myocardial ischemia. The clinical prognostic value of baroreflex sensitivity has already been confirmed in pilot studies conducted by different groups of investigators. Overall, the phenylephrine test has been performed in several hundred patients with no reports of side effects. An ongoing multicenter study, the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) is aimed to definitively assess the predictive value of baroreflex sensitivity and heart rate variability in patients with a prior myocardial infarction. While the enrollment is still ongoing, this study has already provided an important methodological information about the possibility of using non invasive technique to record blood pressure by means of FINAPRES, to evaluate baroreflex sensitivity. Comparison among 142 tests performed with simultaneous recording from an intraarterial line and from FINAPRES indicated a strong correlation (r = 0.9) between the two methods. ATRAMI is expected to close the enrollment in the near future. To data, baroreflex sensitivity appears to be a safe and non-invasive test likely to provide meaningful information on autonomic balance and consequently on risk profile of patients with a prior myocardial infarction.

Animals↗
PubMed1994

Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia.

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P < .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P < .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P < .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.

Acute Disease↗
PubMed1994

Unexpected interaction between beta-adrenergic blockade and heart rate variability before and after myocardial infarction. A longitudinal study in dogs at high and low risk for sudden death.

BACKGROUND: Heart rate (HR) variability is a marker of tonic cardiac autonomic activity and contributes in assessing risk for sudden death after myocardial infarction. Recent clinical observations have indicated that attenuation of HR variability, which occurs after myocardial infarction, may be transient. This study addresses the issue of whether autonomic control of heart rate recovers at different rates after myocardial infarction in subjects at high and low risk for ventricular fibrillation (VF). METHODS AND RESULTS: Thirty dogs, 22 with myocardial infarction and 8 sham-prepared animals, completed the study. Changes and recovery in cardiac autonomic activity after myocardial infarction were examined by measuring HR variability before and at defined intervals during the first 30 days after infarction. Each HR variability measurement was made before and after beta-blockade in dogs at high (n = 10) and low (n = 12) risk for VF. Arrhythmia risk was determined on the basis of development of VF during exercise and transient myocardial ischemia 30 days after infarction. No sham-prepared animals developed VF. Preinfarction measurements of HR variability were not different between the groups before beta-blockade, but HR variability increased much more in response to beta-blockade in animals destined to be resistant compared with susceptible animals (289 +/- 26 to 369 +/- 35 msec, delta 27.7%, versus 270 +/- 36 to 283 +/- 34 milliseconds, delta 4.8%, respectively, P < .01). Immediately after infarction, HR variability was significantly attenuated in all dogs, but in the resistant dogs it recovered to pre-myocardial infarction levels within 10 days. After the infarction, beta-blockade did not increase HR variability in either group of animals. Postoperative increases in HR variability from beta-blockade were preserved in the sham group. Susceptible animals were characterized by a persistent attenuation of HR variability throughout the 30 days. CONCLUSIONS: The depression in HR variability produced by myocardial infarction has a clearly different temporal recovery pattern between low- and high-risk animals. After myocardial infarction, beta-adrenergic blockade does not alter HR variability, thus preserving its predictive value. Before myocardial infarction, however, beta-blockade increases HR variability only in the animals destined to be at low risk for lethal arrhythmias after the infarction. The recovery pattern of HR variability after myocardial infarction may contribute to the early recognition of individuals at high risk for sudden death.

Animals↗
PubMed1993

Pertussis toxin-induced ADP ribosylation of inhibitor G proteins alters vagal control of heart rate in vivo.

Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of Gi and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x 1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals.

Adenosine Diphosphate Ribose↗
PubMed1990

Tocainide and mortality after myocardial infarction: a prospective study in conscious dogs.

The production of an anterior myocardial infarction as part of an experimental animal model for sudden death was burdened by a persistently elevated mortality rate (30%) despite the use of traditional antiarrhythmic drugs. Mortality was reduced when tocainide (600 mg three times daily) was empirically administered for 4 days before and 4 days after myocardial infarction. Retrospective analysis showed that mortality at 4 days after infarction was significantly lower in the tocainide-treated dogs than in the preceding large group of dogs that had not been so treated (5 [9%] of 55, versus 64 [32%] of 199, p less than 0.01). This difference was still evident 30 days after myocardial infarction (13 [24%] of 55 versus 83 [42%] of 199; p less than 0.05). This observation led to the present prospective study in 106 dogs with a similar protocol but with a randomized sequence. At 4 days after myocardial infarction, the mortality rate was 55% lower in the tocainide group than in the control group (7 [12.5%] of 56 versus 14 [28%] of 50; p less than 0.05). During the 10 days after treatment withdrawal 9 (18%) of 49 dogs in the tocainide group died compared with only 2 (5%) of 36 in the control group. This rebound in mortality produced similar survival figures in the two groups at 14 and at 30 days after infarction when mortality was 30% (17 of 56) in the tocainide group and 34% (17 of 50) in the control group. The tocainide plasma levels were 7.4 +/- 4 micrograms/ml the day before infarction and 7.2 +/- 3 micrograms/ml 3 days after infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death.

Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death.

Analysis of Variance↗
PubMed1987

Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface.

The glycosaminoglycan layer of bladder has been proposed to play a crucial role in protecting the bladder from harmful substances in urine. Rats were partially cystectomized to determine whether bladder glycosaminoglycans are routinely eluted from the bladder surface in detectable quantities. Cystectomy produced no detectable qualitative or quantitative changes in excreted GAG thereby showing that most urinary glycosaminoglycan originates in the kidney and not from the bladder. Damaging the glycosaminoglycan layer by a dilute acid wash, however, leads to a consistent decrease in the output of urinary GAG which recovers to normal at the same rate as the layer regenerates. This suggests that the newly exposed sites tightly bind urinary GAG. We suggest that such binding may be a component of the normal physiological defense mechanism of the bladder. The bladder glycosaminoglycan layer was isolated, dilute acid being used to elute ionically-bound material and brief trypsinization to elute intercalated proteoglycans from the luminal surface. The GAG from the luminal surface, which was present at a density of one chain per 50 nm.2 of bladder surface, was quite different in composition from that isolated from the whole bladder.

Animals↗