Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits.

Plasma concentrations of dexmedetomidine (D = 0.1 mg/kg), midazolam (M = 2 mg/kg), and butorphanol (B = 0.4 mg/kg) were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) after their simultaneous (DMB) transnasal (TN) administration to healthy rabbits. Time-dependent changes in sedation and antinociception were evaluated by measuring a sedation score based on rabbit's posture, loss of the righting, palpebral and pedal withdrawal reflexes and by instrumental monitoring of rectal temperature, heart rate, arterial blood pressure, pulse-oximetry, and capnometry. The peak plasma concentration (Cmax ) of each drug was reached within 5 min (Tmax ) from DMB-TN administration along with deep sedation and analgesia. Such effects subsided after 45 min into a moderate sedation and analgesia lasting for additional 15 min. All rabbits awakened spontaneously and uneventfully 90 min after DMB-TN administration. During the anesthetic procedure, arterial blood pressure markedly decreased and respiratory depression ensued requiring oxygen supplementation. The results of this study show that all three molecules of the DMB combination were absorbed through the TN route, inducing deep sedation and analgesia suitable for minor surgical procedures. Such combination should be used with caution in rabbits bearing cardiovascular or respiratory diseases because of its ability to induce hypotension and respiratory depression.

Early assessment of coronary artery bypass graft patency by high-dose dipyridamole echocardiography.

To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiographic testing in the evaluation of coronary artery bypass graft patency early after surgery, 18 consecutive patients with angina underwent dipyridamole echocardiography and coronary angiography before and 7 to 10 days after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and 11 patients, respectively. A total of 53 bypass grafts were performed. Before bypass surgery 14 patients had a positive and 4 a negative test result. No complication occurred during the test performed early after surgery. Of the 14 patients with positive dipyridamole echocardiographic results before surgery, 10 had negative and 4 had positive results after surgery. All 4 patients had negative results before and after surgery. In the 4 patients with positive results after dipyridamole echocardiographic testing before and after bypass surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p = 0.3) after the procedure and wall motion score index at peak dipyridamole changed from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent as seen on angiography. Dipyridamole echocardiographic results were positive in 4 of 5 patients who had at least 1 obstructed graft or native vessel obstructed distal to bypass graft insertion. The remaining patient had diagnostic electrocardiographic changes during dipyridamole infusion without wall motion abnormalities. Dipyridamole echocardiographic results were negative in all 13 patients who had complete revascularization. In the 4 patients with positive test results, the procedure correctly identified the localization of the diseased bypass graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term beneficial effects of PTCA on segmental early relaxation in disease of the left anterior descending coronary artery.

The relationship between regional left ventricular (LV) motion and global pressure relaxation of the left ventricle remains unclear. To clarify the recent concept of segmental early relaxation in coronary artery disease, the authors investigated two groups of patients. In group I, all 12 patients (mean age 47 +/- 7 years) exhibited evidence of a normal heart after an extensive investigation. In group II, 25 patients (55 +/- 7 years) presented an isolated stenosis of the left anterior descending coronary artery, and they underwent a hemodynamic investigation before and after (six to nine months) a durable successful percutaneous transluminal coronary angioplasty (PTCA). After all conventional hemodynamic measurements had been done, a quantitative frame-by-frame analysis of left ventricular wall motion was conducted. The authors' method is derived from that of Ingels, applying to LV cineangiograms filmed in 30 degrees right anterior oblique view at a 50 frames/second rate. Thus segmental wall motion is analyzed in terms of amplitudes (%), velocities of shortening and lengthening in circumferences/second (circ/sec), and times of events (%). Statistical results took into account the reproducibility of the method. Main results regarding the control state of group II consisted of an asynergic motion of the anterior region taking place from end systole to early diastole: 1. Early end of contraction in anterior segments (% of systolic time interval: 88 +/- 14% vs 96 +/- 6% in group I, p less than 0.001) 2. Asynchronism at end systole (maximal velocity of shortening - 0.4 +/- 2.3 circ/sec in anterior segments vs 0.05 +/- 1.9 in inferior segments, p less than 0.02) 3. An early but poor outward anterior wall motion (anterior lengthening at 0.04 sec after the end of ejection 2.9 +/- 10% in group II versus 5.4 +/- 7.2% in group I, p less than 0.05) These abnormalities are strongly correlated with a significant impairment of peak negative diastolic pressure/diastolic time (dP/dt) (1500 +/- 400 mmHg. sec-1 vs 1850 +/- 410 in group I, p less than 0.02). Long-term beneficial effects of PTCA in group II were characterized by an almost complete normalization, both asynergy and relaxation taking place back within the normal range. The authors conclude that in this kind of patient, peak negative dP/dt could be an index of an asynergic segmental motion, this one being correctly analyzed and quantified on LV cineangiograms with our method.

[Isolated stenosis of the left anterior descending coronary artery and regional function of the left ventricle]. / Sténoses isolées de l'interventriculaire antérieure et fonction régionale du ventricule gauche.

This study compared regional and global left ventricular function of a population of patients with a stenosis of the left anterior descending (LAD) artery and a control population in a prospective 18 months protocol. The 25 patients in the LAD group, 21 men and 4 women (55 +/- 9 years), had a pure and isolated stenosis of the LAD artery (70 +/- 8%) without infarction with normal global systolic function. The 12 patients in the control group strictly no cardiovascular disease after extensive investigation. Cardiac catheterisation was carried out in the conventional manner under the same conditions in both groups, after withdrawal of all medication. Regional wall motion was studied on 30 degrees right anterior oblique selective left ventriculography by a technique derived from Ingel's method using every frame of a cycle in terms of amplitude, velocity and time of segmental shortening and lengthening. The patients in the LAD group had normal cardiac function and no hypo or akinesia. The principal characteristic was the finding of anterior wall asynergy which was significantly different from the uneven contraction common in control subjects. This asynergy is observed from the end of systole to early diastole and features: early termination of anterior wall contraction (normalised contraction time: 86 +/- 13% vs 97 +/- 4% in the control group; p less than 0.02; and 90% in the inferior zone, NS, compared with the control group and p less than 0.05 compared with the anterior wall); dephased velocities of segmental shortening at the end of ejection (positive velocities in the inferior zones 0.17 +/- 1.7 circ/sec and negative velocities in the anterior zones, -0.34 +/- 2.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of intracoronary and intravenous urokinase in acute myocardial infarction.

The efficacy of intracoronary and intravenous urokinase was studied in 83 patients with acute evolving myocardial infarction. Urokinase was administered intracoronary in 48 patients with a success rate of 89% obtained after 47 +/- 32 minutes of infusion of a dose of 255.000 +/- 224.000 IU. In-hospital mortality in this group of patients was 10%. Severe arrhythmias were observed in 33% of the patients and the reocclusion rate at the re-study was 16%. Intravenous urokinase was administered as 200.000 IU bolus followed by 1.220.000 IU infusion in 21 patients. Angiography performed in this group of patients 48 hours after therapy showed a patency rate of 66%. A single intravenous bolus of 500.000 IU of urokinase was administered to 14 patients. At angiography all patients but one were found reperfused. The value of intravenous low-dose bolus injection of urokinase in acute myocardial infarction needs hower to be assessed with a properly designed clinical trial.

Electrophysiological study of atrio-ventricular block and ventricular conduction defects. Prognostic and therapeutical implications.

His bundle study with long term follow-up (mean 42 months) was performed in 155 patients (107 with previous syncope, 48 without or with few symptoms). The electrocardiogram showed various conduction abnormalities, but in some cases it was normal. Patients were excluded at the beginning of the study, if they showed sick sinus syndrome, recorded 3rd degree atrioventricular block, angina pectoris, recent myocardial infarction, congenital or surgical cardiac block. In previous studies the diagnostic sensibility and specificity of ajmaline (1 mg/kg/1' i.v.) and overdriving tests have been evaluated. In this study the prognostic meaning of these tests has been evaluated. During a mean 42 months follow-up, 17 patients (10.9%) developed advanced atrioventricular block. A higher risk of developing advanced atrioventricular block below the AV node was detected in patients who showed: basal HV greater than or equal to 65 ms (33% developed advanced atrioventricular block vs 4.7% of patients with basal HV less than 65 ms; p less than 0.001); HV value greater than or equal to 120 ms or 2nd-3rd degree atrioventricular block during ajmaline test (40% progressed to advanced atrio-ventricular block vs 0.85%; p less than 0.001); HV prolonged greater than 10 ms or 2nd-3rd degree atrioventricular block during atrial pacing (40% progressed to a atrioventricular block vs 3.4%; p less than 0.001) regardless of previous syncope.(ABSTRACT TRUNCATED AT 250 WORDS)