We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30-40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs.

Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs.

https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000628

2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

The National ASGE Survey on Upper Gastrointestinal Bleeding: II. Clinical prognostic factors

Marijuana and delta9-tetrahydrocannabinol (THC) increase heart rate, slightly increase supine blood pressure, and on occasion produce marked orthostatic hypotension. Cardiovascular effects in animals are different, with bradycardia and hypotension the most typical response. Cardiac output increases, and peripheral vascular resistance and maximum exercise performance decrease. Tolerance to most of the initial cardiovascular effects appears rapidly. With repeated exposure, supine blood pressure decreases slightly, orthostatic hypotension disappears, blood volume increases, heart rate slows, and circulatory responses to exercise and Valsalva maneuver are diminished, consistent with centrally mediated, reduced sympathetic, and enhanced parasympathetic activity. Receptor-mediated and probably nonneuronal sites of action account for cannabinoid effects. The endocannabinoid system appears important in the modulation of many vascular functions. Marijuana's cardiovascular effects are not associated with serious health problems for most young, healthy users, although occasional myocardial infarction, stroke, and other adverse cardiovascular events are reported. Marijuana smoking by people with cardiovascular disease poses health risks because of the consequences of the resulting increased cardiac work, increased catecholamine levels, carboxyhemoglobin, and postural hypotension.

Cardiovascular System Effects of Marijuana

Serum creatinine concentrations are widely used clinically as an index of renal function. In stable normal or reduced renal function they are determined by the rate of creatinine production and the endogenous creatinine clearance, and, during changing renal function, also by the apparent volume of distribution of creatinine. These determinants of serum creatinine concentrations, however, are affected by age, sex and body weight. The rate of creatinine production is proportional to body weight, and it decreases with age and is slower in females than in males. The endogenous creatinine clearance decreases with age and is lower in females than in males. The apparent volume of distribution of creatinine is equal to the total body water, which is proportional to body weight, and it decreases with age and is lower in females than in males. The individual relationships between the determinants of serum creatinine concentrations and age, sex, and body weight on the relationship between normal and reduced renal function and serum creatinine concentrations are illustrated by simulations. Equations are derived to predict endogenous creatinine clearance from serum creatinine concentrations, and a nomogram is presented for determining relative renal function from serum creatinine concentrations, which take into account the age, sex and body weight of the individual patient. It is recommended for rapid clinical evaluation of stable normal or reduced renal function. When rapid changes are expected clinically, however, it is recommended to use a mid urine collection period serum creatinine sample for creatinine clearance determination.

Use of serum creatinine concentrations to determine renal function.

Thirty-three patients with severe hypertension were treated with rapidly injected intravenous diazoxide. Renal function was measured in nine patients and four underwent cardiac catheterization during renal function studies. Diazoxide had a rapid, profound hypotensive effect. Average decrease in mean arterial pressure was 26%, with an average duration of 16 hours. Drug resistance was not observed. Renal function was not impaired despite maintenance of arterial pressure at or near normal levels. Decreased mean arterial pressure was associated with a decrease in systemic vascular resistance and left ventricular end-diastolic pressure while an increase in cardiac index and heart rate occurred. Urine volume was unchanged, whereas the glomerular filtration rate and the effective renal plasma flow increased but urinary sodium excretion decreased markedly. Intravenous diazoxide is a practical effective agent for treatment of all forms of severe hypertension.

Intravenous Use of Diazoxide in the Treatment of Severe Hypertension

His bundle electrograms were obtained in 42 patients with heart disease before, during and after intravenous isoproterenol infusion. The group consisted of 5 patients with normal conduction and 37 patients with atrioventricular or intraventricular conduction disease. The A-H interval could be measured in 38 patients. In 30 patients with a normal A-H interval ( The following improvements in conduction were noted in the patients with second and third degree atrioventricular (A-V) block during isoproterenol infusion: (1) total reversal of second degree block proximal to the His bundle in two patients; (2) development of 2:1 conduction in one of three patients with third degree A-V block and “split” H potentials; and (3) development of 3:1 conduction in one of three patients with third degree A-V block distal to the His bundle. We conclude that administration of isoproterenol may facilitate both normal and depressed conduction in the A-V node and His-Purkinje system. This effect may lead to partial or total reversal of second or third degree A-V block proximal to, in and distal to the His bundle.

The effect of isoproterenol on atrioventricular and intraventricular conduction.

Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.

Electrophysiologic effects of atropine on human sinus node and atrium

Pre-excitation with Normal PR Intervals: A Case Secondary to Slow Kent Bundle Conduction

We have previously reported that 25 micrograms/kg of intravenous (i.v.) delta-9-tetrahydrocannabinol (delta-9-THC) produces marked increases in heart rate, prolongation of left ventricular ejection time corrected for heart rate (LVETc), and a shortening of the pre-ejection period in normal volunteers. Beta-adrenergic blockade partially attenuates these responses. To elucidate further the mechanism of action of delta-9-THC, we gave 10 normal volunteers 0.1 mg/kg of i.v. propranolol and 2 mg of i.v. atropine before they received 25 micrograms/kg of i.v. delta-9-THC. Systolic time intervals were compared in the denervated subjects before and after delta-9-THC. Post delta-9-THC responses were measured at a time approximating peak psychologic high. Mean +/- SEM heart rate before and after delta-9-THC was 89 +/- 4 and 87 +/- 3 beats/min (NS); mean +/- SEM pre-ejection period before and after delta-9-TCH was 107 +/- 5 and 109 +/- 4 ms (NS); and mean +/- SEM LVETc before and after delta-9-THC was 433 +/- 6 and 429 +/- 6 ms (NS). Since previous denervation of our subjects with atropine and propranolol totally abolished changes in heart rate and systolic time intervals, the cardiac effects of delta-9-THC appear to be mediated totally via the autonomic nervous system, probably reflecting direct central nervous system stimulation.

J. Maurice Pouget

Papers

Intravenous Use of Diazoxide in the Treatment of Severe Hypertension

The effect of isoproterenol on atrioventricular and intraventricular conduction.

Electrophysiologic effects of atropine on human sinus node and atrium

Pre-excitation with Normal PR Intervals: A Case Secondary to Slow Kent Bundle Conduction

Lack of cardiovascular effects of delta-9-tetrahydrocannabinol in chemically denervated men.