Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium.

Irradiation of isolated cardiac muscle by high-power, high-frequency, continuous wave ultrasound selectively damages endocardial endothelium (EE). We evaluated this ultrasound effect in vivo on the performance of the intact ejecting canine left ventricle (LV). A cylindrical ultrasound probe (0.9 MHz, 25 W), mounted on a catheter, was inserted in the LV cavity through an apical stab wound and was activated for 60, 120, and 240 s, followed each time by a recovery period of 10-15 min. Ultrasound transiently and repeatedly abbreviated the time interval from end diastole to peak (-)dP/dt (from 241 +/- 30 to 229 +/- 32 ms after 240 s; P < 0.001), accelerated LV pressure fall, did not alter peak (+)-dP/dt or peak systolic pressure, increased diastolic and systolic segment lengths, and decreased fractional shortening. Microscopic analysis revealed dispersed granulocytes attached to the EE. EE cells were visibly damaged only in a limited area surrounding the probe. Accordingly, high-power, high-frequency, continuous wave ultrasound reversibly modulated LV performance, presumably by transient alteration of EE function.

Effects of ketanserin, a 5-HT2-receptor antagonist, on the blood flow response to temperature changes in the diabetic foot.

We studied the effect of ketanserin, a relatively specific antagonist for 5-hydroxytryptamine2-serotonergic receptors, on the total blood flow to the foot of patients with diabetes using a computerized pulse volume plethysmograph and a temperature controlled foot chamber. Ketanserin was administered intravenously as a bolus of 10 mg over four minutes followed by a constant infusion at the rate of 5 mg/hr. Saline infusion served as a control in each subject. Sixteen patients with type II diabetes and two patients with type I diabetes were studied. Mean age was 58.5 +/- 1.6 years and mean duration of diabetes was 10 +/- 2 years. Basal blood flow (mean +/- SEM, mL/100 mL/min) at room temperature was 3.77 +/- 0.99 with saline and 12.07 +/- 1.81 with ketanserin. At 38 to 40 degrees C, the values were 4.84 +/- 1.09 and 16.93 +/- 1.83. Reactive hyperemia was measured following three minutes of arterial occlusion; at 38 to 40 degrees C the flow rate was 20.67 +/- 2.45 with saline and 30.86 +/- 3.02 with ketanserin, while at 8 to 10 degrees C the corresponding values were 15.63 +/- 2.01 and 27.16 +/- 2.03. All differences between saline and ketanserin had a P less than .01. Venous distensibility (vol% at 50 mm Hg) at 8 to 10 degrees C was 0.55 +/- 0.05 with saline and 0.90 +/- 0.15 with ketanserin, P less than .05. Our findings are consistent with the hypothesis that serotonin is involved in the limitation of blood flow to the foot in diabetes and that ketanserin may play a potential role in therapy.

Treatment of Raynaud's phenomenon with ketanserin, a selective antagonist of the serotonin2 (5-HT2) receptor.

Ketanserin, a selective antagonist of the 5-HT2 receptor, was evaluated in a 4-week open pilot trial of 30 patients with Raynaud's phenomenon. Moderate or marked relief was reported in 15 of 18 (83%) patients with systemic sclerosis, whereas only 4 of 12 (33%) patients with Raynaud's phenomenon of other etiology received such benefit (P less than 0.01). These subjective ratings were supported by the results of serial digital strain gauge plethysmography during controlled cold challenge. Additional clinical findings suggested that ketanserin therapy facilitated the healing of ischemic digital ulcerations and reduced hand edema in patients with systemic sclerosis. These findings lend support to the hypothesis that serotonin is an important element in the pathogenesis of systemic sclerosis.

Plethysmographic registration of volume changes in a hand vein. Effects of serotonin and of a specific antagonist.

The influence of serotonin on a selected dorsal hand vein can be evaluated by changes in tangential wall tension, volume, and pressure. A plethysmographic method has been used to record the changes in venous capacitance at constant pressure after IV injection of small doses of serotonin. R 41 468, a specific serotonin antagonist, has been given orally (10, 20, or 40 mg) or intravenously (2.5 or 10 mg) to healthy volunteers. A reduction or a complete blockade of activity of serotonin was observed after all doses of R 41 468. Duration and strength of the antagonism were dose-dependent. This pharmacologic in vivo model allows investigations into substances with an effect on vascular smooth muscles.

Thalamonal, droperidol and fentanyl in induced hypovolaemic shock in the conscious dog.

Previous studies had shown that Thalamonal exerts a protective activity against hypovolaemic shock in experimental animals as well as in patients. The purpose of the present study was to make a long-term evaluation of the value of single doses of Thalamonal fentanyl and droperidol as shock-protecting agents in conscious dogs which received no replacement of blood loss. The study was conducted in 20 animals in which devices were implanted for measuring heart rate, arterial and venous blood pressure, left ventricular and left atrial blood pressure. The dogs were divided into 4 groups, receiving 20 ml of an i.v. injection containing either 0.025 mg/kg fentanyl, 0.625 mg/kg droperidol, 0.25 ml/kg Thalamonal (0.625 mg/kg droperidol + 0.0125 mg/kg fentanyl), or saline. Thalamonal allowed a 100 per cent survival of the dogs, one of the 5 animals survived in the droperidol group, whereas fentanyl and saline were completely ineffective. As a possible mechanism of action the interruption of the vicious sequence of blood loss, vasoconstriction and circulatory arrest at a peripheral and/or central level is discussed. The hypothesis of intracorporeal blood volume correction under the influence of Thalamonal as an anti-vasoconstrictor seems to be logical but needs further investigation.

Intermittent claudication: a controlled study in parallel time of the short-term and long-term effects of cinnarizine.

In a group of 45 patients with mild to moderately severe claudication studied over the same 4-month period, cinnarizine administration (75 mg 3-times daily) was associated with a greater than 20% improvement in walking distance in 65% of the patients, who derived significantly more benefit than the 30% of placebo responders. The mean improvement in walking distance was 11% for the placebo group compared to 142% for cinnarizine-treated patients. An open 12-month follow-up showed that improvements in walking distance with cinnarizine were maintained in all 12 patients, whereas in the 10 control patients only 10% reported improvement. Objectively, significant plethysmographic improvements were detected only for the cinnarizine-treated patients and shown by an increase in arterial flow-pressure dynamics of the lower limbs.

An improved animal model for studying the effect of drugs on myocardial metabolism during ischemia.

An improved dog model to study the effect of drugs on myocardial metabolism during ischemia is described. A reproducible degree of ischemia could be obtained by partial occlusion of the anterior descending branch of the left coronary artery (LAD), using an inflatable cuff with a micrometer. The possibility of inducing the stenosis twice in the same animal has the advantage that the animal can be used as its own control. The reproducibility of the degree of ischemia was demonstrated by the nonsignificant differences in local venous lactate, inorganic phosphate, and glucose concentrations after the first and second stenosis. The mean pressure difference over the stenosis was used to express the degree of coronary artery narrowing. In this model, one does not have to rely on the collateral circulation in collecting local venous blood. Moreover, it is very likely that this blood is obtained from the most pronounced ischemic area, which was localized with radioactive microspheres. At this degree of stenosis, left ventricular function was not affected too much, as was demonstrated by the slight changes in dP/dt max, and systolic and diastolic aortic pressure after induction of the stenosis. The usefulness of our model to evaluate the activity of drugs is demonstrated by the effect of fentanyl, a potent morphine-like analgesic, on the poststenotic local venous lactate and inorganic phosphate concentrations.

The radioactive microsphere method for the assessment of regional myocardial blood flow after coronary artery occlusion. Inaccuracies due to variations in the diameter distribution of the spheres.

In this study, we have tried to determine the magnitude of the inaccuracy of the radioactive microsphere method - due to variations in the diameter distribution of the spheres - for measuring regional myocardial blood flow after coronary artery occlusion. In 5 mongrel dogs, three types of 15 mum microspheres, labelled with 125I, 141Ce or 85Sr, were injected simultaneously after the descending branch of the left coronary artery had been ligated. Myocardial samples wert taken from the left ventricle and divided into four groups according to the number of spheres per sample. The radioactivity of the various isotopes per gram tissue was expressed as percentage of their activity per milliliter of the reference sample. The diameter distribution of microspheres, labelled with each of the isotopes, was determined light-microscopically in suspensions belonging to three different batches. The relative error, as determined from the difference in relative radioactivity of the various types of microspheres in the tissue samples, was higher than the theoretical error for each of the number of spheres per sample. It is very likely that this discrepancy is caused by the differences in diameter distribution of the various types of microspheres, resulting in non-random error. The smaller spheres tended to go to low flow areas and the larger ones to high flow areas. Because of the non-randomness, the error due to diameter variations in the spheres can be diminished by randomizing the order of injection of the various isotopes. The present study indicates that the relatively high degree of accuracy of the microsphere method for the determination of blood flow to large parts of the myocardium with an unimpeded coronary circulation, as was described in literature, cannot be extrapolated to the determination of regional myocardial blood flow after coronary artery occlusion, when the combination of small tissue samples, variations in the diameter distribution of the spheres and an unevenly distributed myocardial blood flow unfavourably affect the accuracy of the method.