Thermal panting in dogs: the lateral nasal gland, a source of water for evaporative cooling.

Two lateral nasal glands appear to provide a large part of the water for evaporative cooling in the panting dog; their function is analogous to that of sweat glands in man. Each gland drains through a single duct which opens about 2 centimeters inside the opening of the nostril. This location may be essential to avoid desiccation of the nasal mucosa during thermal panting. The rate of secretion from one gland increased from 0 to an average of 9.6 g (gland . hour)(-1) as air temperature was increased from 10 degrees to 50 degrees C. Evaporation of the fluid from the paired glands could account for between 19 and 36 percent of the increase in respiratory evaporation associated with thermal panting. The fluid secreted by the gland was hypoosmotic to plasma.

Exercise performance-based outcomes of medically treated patients with coronary artery disease and profound ST segment depression.

OBJECTIVES: We sought to determine the relationship between exercise duration and cardiovascular outcomes in patients with profound (> or =2 mm) ST segment depression during exercise treadmill testing (ETT). BACKGROUND: Patients with stable symptoms but profound ST segment depression during ETT are often referred for a coronary intervention on the basis that presumed severe coronary artery disease (CAD) will lead to unfavorable cardiovascular outcomes, irrespective of symptomatic and functional status. We hypothesized that good exercise tolerance in such patients treated medically is associated with favorable long-term outcomes. METHODS: We prospectively followed 203 consecutive patients (181 men; mean age 73 years) with known stable CAD and > or =2 mm ST segment depression who are performing ETT according to the Bruce protocol for an average of 41 months. The primary end point was occurrence of myocardial infarction (MI) or death. RESULTS: Eight (20%) of 40 patients with an initial ETT exercise duration < or =6 min developed MI or died, as compared with five (6%) of 84 patients who exercised between 6 and 9 min and three (3.8%) of 79 patients who exercised > or =9 min (p = 0.01). Compared with patients who exercised < or =6 min, increased ETT duration was significantly associated with a reduced risk of MI/death (6 to 9 min: relative risk [RR] = 0.25, 95% confidence interval [CI] 0.08 to 0.76; >9 min: RR = 0.14, 95% CI 0.04 to 0.53). This protective effect persisted after adjustment for potentially confounding variables. We observed a 23% reduction in MI/death for each additional minute of exercise the patient was able to complete during the index ETT. CONCLUSIONS: Optimal medical management in stable patients with CAD with profound exercise-induced ST segment depression but good ETT duration is an appropriate alternative to coronary revascularization and is associated with low rates of MI and death.

The effect of caffeine on ventricular ectopic activity in patients with malignant ventricular arrhythmia.

We evaluated the effect of caffeine on ventricular ectopic activity in a group of 50 consecutive patients with malignant ventricular arrhythmia. The clinical arrhythmia in these patients (mean age, 61 years) was recurrent ventricular tachycardia in 21 (42%), ventricular fibrillation in three (6%), and symptomatic nonsustained ventricular tachycardia in 26 (52%). Forty-two (84%) had either ischemic heart disease or cardiomyopathy. Each patient underwent two short-term drug trials on successive days, receiving either decaffeinated coffee mixed with 200 mg of caffeine or the decaffeinated drink alone. Continuous electrocardiographic recordings were made during the 30-minute control period, the three-hour observation period, and the hourly bicycle exercise tests. Forty-five patients (90%) exhibited ventricular couplets and 29 patients (58%) had salvos of ventricular tachycardia during the testing. However, no differences between the caffeine and decaffeinated trials were observed in either individual or group data on total or repetitive ventricular arrhythmia. Serum catecholamine levels reflected the average increase in serum caffeine level but were not associated with enhanced arrhythmia. We found no evidence that a modest dose of caffeine is arrhythmogenic, even among patients with known life-threatening arrhythmia.

Precordial mechanical stimulation for exposing electrical instability in the ischemic heart.

Sequenital mechanical pulsing of the chest wall with three stimuli failed to induce arrhythmias in normal dogs. After coronary arterial occlusion, this technique evoked in 11 of 12 animals repetitive ventricular tachycardia in 2. These responses corresponded closely to those elicited by electrical testing. In four conscious animals after recovery from myocardial infarction, precordial pulsing induced repetitive ventricular arrhythmias. The type of arrhythmia produced depended on the degree of prematurity of the third pulse in the sequence. The use of precordial mechanical stimulation can perhaps be modified and adapted as a method of detecting persons at high risk for sudden cardiac death.

Acute blood pressure elevation and ventricular fibrillation threshold during coronary occlusion and reperfusion in the dog.

The effect of acute elevation of arterial blood pressure on the ventricular fibrillation threshold was examined in 19 closed chest dogs anesthetized with chloralose during 10 minutes of occlusion followed by abrupt reperfusion of the left anterior descending coronary artery. Ventricular fibrillation threshold was determined using two methods of electrical testing: sequential R/T pulsing and the train of stimuli method. Blood pressure was increased with an intravenous injection of the alpha adrenergic stimulator phenylephrine. Acute hypertension significantly diminished the enhanced vulnerability associated with coronary occlusion. After denervation of the carotid sinus and aortic arch baroreceptors, elevation of blood pressure failed to affect vulnerability during occlusion. In both intact and denervated animals, the predisposition to ventricular fibrillation after reperfusion was unchanged by the increase in blood pressure. It is suggested that withdrawal of sympathetic tone mediated by the baroreceptor reflex is the basis for the protection against ventricular fibrillation resulting from elevation of blood pressure. The failure of acute hypertension to alter vulnerability during reperfusion suggests that the predisposition to ventricular fibrillation during reperfusion is due to mechanisms other than those operating during coronary occlusion.

Aggravation of arrhythmia by antiarrhythmic drugs--incidence and predictors.

Aggravation of arrhythmia by antiarrhythmic drugs is a potentially serious complication. In over 1,287 noninvasive drug studies involving 11 antiarrhythmic drugs, arrhythmia aggravation occurred in 117 tests (9%). During 248 electrophysiologic tests, 45 cases (18%) of aggravation occurred. In an attempt to define predictors of this complication, 51 patients with aggravated arrhythmia were compared with 102 patients without this complication. Arrhythmia aggravation was not associated with age, sex, type or extent of heart disease, baseline electrocardiogram, drug-induced changes on electrocardiogram or density of baseline arrhythmia on monitoring or exercise testing. Aggravation with 1 drug did not predict occurrence with another drug of the same class. The only statistically important relation was the type of presenting arrhythmia. Patients with a history of a sustained tachyarrhythmia (ventricular tachycardia or ventricular fibrillation) had a risk of this complication that was 2.5 times greater than that of patients presenting with only nonsustained ventricular tachycardia or ventricular premature beats (p = 0.01). There was also a relation to the presence of left ventricular dysfunction (p = 0.04). For the most part, however, aggravation of arrhythmia is not predictable, and cautious use of antiarrhythmic drugs is essential.

Determinants of survival in patients with malignant ventricular arrhythmia associated with coronary artery disease.

The long-term survival data in patients with coronary artery disease and a history of malignant ventricular arrhythmia, defined as noninfarction ventricular fibrillation (VF) or hemodynamically compromising ventricular tachycardia (VT) followed for up to 9 years, were analyzed. In this group of 161 patients there was a total of 57 deaths, of which 35 (63%) were sudden. Life-table analysis demonstrated a 10% sudden death rate for all patients in the first year and a 7% annual rate in the subsequent 4 years. In patients managed noninvasively, the overall mortality rate was 27% over 9 years, or 3% per year. Suppression of ventricular tachycardia on both ambulatory monitoring and exercise testing was associated with improved survival. In patients evaluated by electrophysiologic testing the sudden death rate was 1.4% per year over an average of 5 years. This survival rate was not different compared with the noninvasive group (p = 0.09). Measures of left ventricular dysfunction and the frequency of ventricular arrhythmia before and after drug therapy were associated with a risk of sudden cardiac death by univariate analysis. Multivariate regression analysis identified 4 variables as independent predictors of sudden cardiac death: rales (p = 0.009), the number of runs of VT during exercise testing while receiving antiarrhythmic drug therapy (p = 0.0003), a history of congestive heart failure (p = 0.0009) and the number of premature beats on Holter monitoring (p = 0.01). These findings support the concept that suppression of repetitive arrhythmia on Holter monitor and exercise testing is a marker for improved survival among patients with malignant ventricular arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden cardiac death--an approach to management of the patient at risk.

Sudden cardiac death due to ventricular fibrillation is the most common cause of death in industrialized countries. Patients with an increased risk of sudden cardiac death may be found to have, in addition to high-grade ventricular arrhythmias, impaired left ventricular function. Mechanisms responsible for precipitation of ventricular fibrillation include risk factors such as increased sympathetic nervous system activity, electrolyte disturbances, coronary artery spasm and transient, thrombotic coronary artery occlusion. For detection of high-grade arrhythmias as well as for assessment of treatment, continuous 24-hour EKG monitoring and exercise EKG should be employed. The indication for antiarrhythmic therapy should be regarded as established in patients successfully resuscitated after unexpected ventricular fibrillation as well as in patients status-post myocardial infarction, with angina pectoris, cardiomyopathies, QT-prolongation, mitral valve prolapse, congenital or other markedly symptomatic heart disease and high-grade ventricular arrhythmias. The treatment initiated, after discontinuation of all antiarrhythmic drugs for at least four half lives and ambulatory EKG monitoring for 48 hours as well as maximal symptom-limited exercise testing, should be evaluated after acute drug administration and after 72 hours of maintained therapy with the aid of continuous EKG monitoring and exercise EKG. In patients with a history of malignant arrhythmias in whom no evidence of high-grade ventricular arrhythmias can be found in either the continuous EKG recording or in the exercise EKG, initiation of drug treatment should be based on the results of programmed electrical stimulation. Effective treatment can be assumed on documentation of complete suppression of arrhythmias grade IVb and V or prevention of precipitation of ventricular tachycardias, respectively, as well as 90% reduction of grade IVa and 50% reduction of premature ventricular beats. During acute testing, aggravation of arrhythmias after administration of antiarrhythmic drugs was seen in 11.1%. While the yearly mortality of successfully controlled patients ranged between 2.3 and 2.8%, the yearly mortality rate in those in whom the arrhythmias were inadequately controlled ranged from 43.6 to 56%.

Central serotonergic agents raise the repetitive extrasystole threshold of the vulnerable period of the canine ventricular myocardium.

Systemic administration of three central serotonergic agents, melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), produced significant increases in the threshold of the vulnerable period for repetitive electrical activity in the canine cardiac ventricle. MK-212 was effective despite bilateral vagotomy. The specific serotonin antagonist, metergoline, blocked the effect of MK-212 on the threshold. An increase in central serotonergic activity may inhibit the flow of arrhythmogenic sympathetic nerve traffic from the brain to the heart.

Results of a second-opinion trial among patients recommended for coronary angiography.

OBJECTIVE: To assess the feasibility of carrying out a second-opinion trial for patients urged to undergo coronary angiography and to assess the long-range outcome of such patients denied that procedure, and the criteria evolved for reaching such a conclusion. DESIGN: A case series of patients referred for a second opinion as to the need for coronary angiography. Patients were followed up by questionnaire, telephone call, and center visits. SETTING: Cardiovascular referral center and teaching hospital in Boston, Mass. PATIENTS: One hundred seventy-one patients with coronary artery disease (144 men, average age 60 years; range, 36 to 88 years). Three patients became unavailable for follow-up during a mean of 46.5 months. OUTCOME MEASURES: Concordant-discordant outcome as to the second opinion, cardiac events, invasive interventions, quality of life questionnaire, and level of symptoms. RESULTS: One hundred thirty-four (80%) of the 168 patients were judged not to require angiography; it was recommended in six. In 28 (16%) recommendation was deferred pending further studies. At a mean follow-up of 46.5 months among the 168 patients, there were seven cardiac deaths (annualized cardiac mortality of 1.1%); 19 patients experienced a new myocardial infarction (2.7% annualized rate), while 27 patients (4.3%) were judged to have developed unstable angina. Twenty-six patients (15.4%) ultimately underwent either coronary bypass or angioplasty. CONCLUSIONS: In a large fraction of medically stable patients with coronary disease who are urged to undergo coronary angiography, the procedure can be safely deferred. While there may be a limitation in terms of generalizing this experience to all patients with coronary disease, we reasonably conclude that an estimated 50% of coronary angiography currently being undertaken in the United States is unnecessary, or at least could be postponed.

Results of a second-opinion program for coronary artery bypass graft surgery.

Second opinions for surgical procedures are now being sought by patients or are required by insurance carriers. We examined outcomes among 88 patients (76 men; average age, 59 years) referred for a second opinion as to the need for coronary artery bypass graft surgery. All patients had undergone coronary arteriography, which disclosed in 63 (72%) multivessel coronary artery disease, while in the remaining 25 patients single-vessel disease involved the left anterior descending coronary artery. Continuation of medical therapy was recommended for 74 (84%) of the 88 patients. Sixty of these 74 patients chose this option and continued to receive medical therapy without any fatalities during a follow-up period of 27.8 months. The remaining 14 patients elected to cross over to surgical therapy at an average of 11.3 months from the second opinion. We conclude that second opinions for selected, motivated patients slated for coronary artery bypass graft operation afford a significant and safe option. Moreover, a majority of patients will adhere to a second opinion recommending medical therapy, thus reducing the need for surgical intervention by as much as 50%. Since the study was based on a small sample size of self-selected patients, these data require caution in extrapolating to the general population with coronary artery disease.

Relationship between ease of inducibility of arrhythmia with electrophysiologic testing and response to antiarrhythmic therapy.

Electrophysiologic studies are an important tool for guiding the selection of an effective antiarrhythmic drug. The purpose of this study was to determine if there was a relationship between the number of extrastimuli necessary to induce arrhythmia and the response to antiarrhythmic drugs. A group of 56 patients with sustained ventricular tachycardia or ventricular fibrillation who were inducible underwent 235 single-drug studies (4.2 per patient). During the control study, one extrastimulus provoked an end point in 12 patients (group 1) and in only two patients (17%) was at least one drug effective. Of the 18 patients requiring two extrastimuli for induction during baseline (group 2), at least one drug was effective in 11 patients (61%). At least one drug was effective in 20 of 26 patients (77%) who required three extrastimuli (group 3). There were no significant differences among the three groups with respect to presenting arrhythmia, presence of coronary artery disease, or left ventricular ejection fraction. When single drugs or a combination of drugs were used, 58% of group 1, 72% of group 2, and 85% of group 3 were rendered noninducible. During a follow-up of 28 to 32 months, yearly recurrence of arrhythmia was 9.4%, 4.6%, and 1.7%, for the three groups, respectively.

Signal averaging technique for noninvasive recording of late potentials in patients with coronary artery disease.

An advanced non invasive signal averaging technique was used to detect late potentials in two groups of patients: Group A (24 patients) with coronary artery disease (CAD) and without sustained ventricular tachycardia (VT) and Group B (8 patients) with CAD and sustained VT. Recorded analog data were digitized and aligned using a cross correlation function with fast Fourier transform schema, averaged and band pass filtered between 60 and 200 Hz with a non-recursive digital filter. Averaged filtered waveforms were analyzed by computer program for 3 parameters: (1) filtered QRS (fQRS) duration (2) interval between the peak of the R wave peak and the end of fQRS (R-LP) (3) RMS value of last 40 msec of fQRS (RMS). Significant change was found between Groups A and B in fQRS (101 -/+ 13 msec vs 123 -/+ 15 msec; p < .0005) and in R-LP vs 52 -/+ 11 msec vs 71-/+18 msec, p <.002). We conclude that (1) the use of a cross correlation triggering method and non-recursive digital filter enables a reliable recording of late potentials from the body surface; (2) fQRS and R-LP durations are sensitive indicators of CAD patients susceptible to VT.