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Biomedical subjects

F Crea

Publications and source records attributed to F Crea.

At least 199 records · Page 11Linked to original sources

A comparative study of laser beam characteristics in blood and saline media.

Little information is available concerning the influences on laser radiation exerted by the various media through which lasing is done. The effects of saline solution and blood on argon laser beam divergence and projection were studied. In addition, the resulting effects on arterial tissue were evaluated after lasing through these media. This was performed with the fiber tip held in various positions relative to the arterial wall. The presence of blood, even in a diluted form, increased beam divergence and reduced forward projection. Perpendicular lasing through saline solution resulted in crater diameters similar in size to the core diameter of the fiber used irrespective of energy levels (424 +/- 97 microns at energy = 2 W X 5 seconds and 490 +/- 80 microns at energy = 2 W X 10 seconds). In contrast, lasing through blood produced much wider craters that increased in size with the higher energy level (878 +/- 215 microns at 2 W X 5 seconds and 1,294 +/- 314 microns at 2 W X 10 seconds). Arterial wall damage could also be inflicted at a greater distance when lasing through blood than through saline solution. Lasing arterial tissue through blood with the fiber tip held parallel to and in contact with the arterial wall resulted in wide craters when lasing was performed in a "static" as well as a "dynamic" fashion. Lasing through saline solution in these positions produced no visible damage to the arterial wall. These results provide some guidelines that may be useful in the clinical application of Argon laser revascularization.

Arteries↗

Effects of verapamil in preventing early postinfarction angina and reinfarction.

Because verapamil is effective in the treatment of "preinfarction" angina, a single-blind, placebo-controlled trial was performed in 17 patients admitted to the coronary care unit with transmural acute myocardial infarction (AMI) to assess the effects of verapamil on angina and reinfarction after AMI. The study was terminated because results obtained in the initial 17 patients indicated that verapamil is not as effective in treating angina after AMI as it is in angina before AMI and does not prevent reinfarction. Continuous electrocardiographic monitoring during the first 3 days after AMI showed the presence of transient episodes of ST-segment elevation in 4 patients taking verapamil and 4 patients taking placebo. The total number and duration of transient ischemic episodes was similar in the 2 groups (46 vs 41 and 23 +/- 22 vs 17 +/- 15 minutes, respectively). The percentage of transient ischemic episodes accompanied by chest pain was similar in both groups (10%). The ischemic episodes were never preceded by important increases of heart rate. Four patients taking verapamil and 4 taking placebo had reinfarction within the first 10 days after the incident AMI. These findings suggest that the prevailing mechanisms of myocardial ischemia in the immediate post-AMI period could be different from those operating in angina before AMI.

Aged↗

"Hot tip": another method of laser vascular recanalization.

UNLABELLED: This study is a preliminary report evaluating the use of laser radiation to heat a metal-capped fiber for arterial recanalization. The method was compared to the currently used bare-ended fiber for recanalization of occluded vessels. The model used was a human coronary artery xenograft transplanted in the femoral artery of the dog. At 4 weeks following the transplantation, laser recanalization was attempted using the heated metal probe ("hot tip") in five arteries and the bare fiber in another five arteries. RESULTS: 1) Angiography demonstrated recanalization in all five arteries treated with the "hot tip" and three of the five arteries treated with the bare fiber. 2) Only one perforation occurred with the "hot tip," whereas three perforations occurred with the bare fiber. 3) The larger metal cap was capable of creating a wider channel in the occluded arterial segment. Although the trend favored the heated metal cap in terms of recanalization and less perforation than the bare fiber, the total number of experiments were not adequate to demonstrate statistical significance. Microscopic examination of the vessels recanalized by either technique was similar. Characteristic charring at the recanalization site was seen regardless of the technique used. These observations suggest that the effect of direct laser radiation on plaques is predominantly a thermal effect. Although these results would suggest utilization of a metal-capped fiber for vascular recanalization, more studies need to be done to confirm these preliminary findings.

Animals↗

Failure of experimental atherosclerosis to sensitize coronary arteries to spasm in hypercholesterolemic rabbits.

Since hypercholesterolemia sensitizes isolated rabbit coronary arteries to vasoconstrictor stimuli, we assessed the possibility of reproducing occlusive coronary spasm both in vitro and in vivo in atherosclerotic rabbits. In Langendorff-perfused hearts from nine atherosclerotic rabbits (2% cholesterol diet for 18 weeks), despite a threefold increase of cholesterol concentration in the coronary wall compared with nine control rabbits, ergonovine and serotonin did not produce any increase of coronary vascular resistances; the increase produced by pitressin was significantly less in atherosclerotic than in normal hearts (56 +/- 13% vs 138 +/- 28%, p less than 0.05, respectively), whereas that produced by phenylephrine was similar (10.1 +/- 1.8% vs 8.5 +/- 2.4%, p = n.s.). In eight other unanesthetized rabbits we recorded the ECG during ergonovine administration (0.05 mg/kg) and during hypothalamic stimulation before and at regular intervals during the 2% cholesterol diet; rabbits survived for periods ranging from 1 to 22 weeks (mean 9.6 weeks). Only one animal had ST depression during episodes of marked tachycardia; no ischemic ECG changes were ever observed in the other rabbits despite the diffuse subintimal coronary deposition of cholesterol found postmortem. Thus, in atherosclerotic rabbits with chronic marked hypercholesterolemia, coronary arteries do not develop occlusive coronary spasm as observed in patients with variant angina.

Animals↗

Influence of the chosen model of stenosis on pressure-flow relationships in isolated perfused arteries.

Passive changes in luminal diameter caused by a fall in the intravascular distending pressure at the site of a severe coronary artery stenosis were recently proposed as a possible cause of transient myocardial ischaemia. We tested this hypothesis in 5 dog carotid arteries perfused with blood at a constant inflow (100 mm Hg) and variable outflow pressures (40-0 mm Hg). Similar degrees of stenosis were induced either with an external circumferential snare or with an intravascular fluid-filled balloon catheter. In 39 experiments outflow pressure was progressively decreased from 40 to 0 mm Hg. This was done first in the absence of stenosis, secondly with an external stenosis (snare) and finally with an internal stenosis of comparable severity (fluid-filled balloon). When stenosis was absent or intraluminal, flow increased progressively from 109.1 +/- 39 to 136 +/- 55 ml/min (P less than 0.06) and from 23 +/- 16 to 34.2 +/- 16 ml/min (P less than 0.001), respectively. Resistance also rose because flow increased proportionally less than the pressure gradient. Conversely, when stenosis was produced by a snare, flow decreased progressively, from 23.9 +/- 17 to 10.7 +/- 15 ml/min (P less than 0.001). Assuming the reduction of flow was caused by the external stenosis compressing the wall into the lumen (against the intravascular pressure) we prepared an artificial vessel with a foam rubber wall inside a silastic tubing. In this artificial vessel (but not in a glass model) a snare stenosis caused reduction in flow when outflow pressure was lowered. Passive changes in caliber due to a reduced distending pressure do not therefore appear to be a cause of flow reduction.

Animals↗

In vitro effects of argon laser radiation on blood: quantitative and morphologic analysis.

Use of the argon laser to recanalize stenosed arteries may require delivery of the beam through blood. To assess the degree of hemolysis and debris formation, 84 samples of citrated whole blood were exposed to argon laser radiation with varying power (1, 2 and 3 watts) and duration (5, 10, 20 and 40 seconds). Compared with control samples, only blood samples exposed to a power of 3 watts for 40 seconds showed a marked decrease in hematocrit (from 37 +/- 1.3 to 33 +/- 1.4%, p less than 0.01) and a marked increase in both free hemoglobin concentration (from 0.2 +/- 0.2 to 1.3 +/- 0.5 g/100 ml, p less than 0.01) and debris weight (from 0.9 +/- 0.3 to 2.8 +/- 0.5 mg, p less than 0.01). Scanning electron microscopy of debris from samples of whole blood, washed erythrocytes and platelet-rich plasma lased at 3 watts for 40 seconds documented the presence of membrane denaturation of blood elements, resulting in their fusion to form complex mesh-like conglomerates. Similar morphologic changes were observed in whole blood samples exposed to a "hot tip" rather than laser radiation. These data indicate that: 1) argon laser radiation with a power of 3 watts does not produce apparent hemolysis or debris formation for exposure periods up to 20 seconds, and 2) the effects of laser radiation on blood are probably mediated by thermal denaturation of cell membranes, as suggested by the same morphologic changes produced by thermal injury from a "hot tip."

Argon↗

Laser recanalization of acutely thrombosed coronary arteries in live dogs: early results.

Laser recanalization was attempted in thrombosed coronary arteries of 10 dogs. In all dogs a coronary thrombus was obtained by passing a low grade electrical current through a guide wire advanced into the artery. Recanalization was then attempted using an argon laser with energy levels ranging from 3 to 30 J. In six dogs a 140 micron core optical fiber was positioned proximal to the thrombus and lasing was done during fiber advancement. The thrombosed artery was recanalized in one dog, perforated in four and neither recanalized nor perforated in one. In the remaining four dogs a steerable guide wire was advanced across the thrombus and a catheter was passed over the guide wire and exchanged for a 200 micron core optical fiber. After fiber withdrawal, mechanical recanalization without lasing was performed in one of the four dogs. In the remaining three dogs, both the fiber and the catheter were again advanced distal to the thrombus and lasing was done during withdrawal; this caused coronary perforation in all dogs. Laser recanalization of thrombosed coronary arteries in dogs using currently available techniques is feasible but results in a very high incidence of perforation.

Acute Disease↗

Laser recanalization of occluded atherosclerotic arteries in vivo and in vitro.

Controlled laser irradiation was used to recanalize atherosclerotic stenoses in vivo and in vitro. In 15 rabbits with atherosclerotic arteries a catheter was positioned in the distal aorta for angiographic examination and as a guide for a small silica optical fiber. Both Nd-YAG and argon lasers were used for recanalization with varying power and duration. As determined by angiographic studies the severity of iliofemoral stenoses in eight 15 arteries decreased from 78 +/- 18% to 32 +/- 11% (mean +/- SD). In one additional artery the stenosis improved from 45% to 25%, but this was associated with perforation. The other six arteries were perforated (two after fiber manipulation, four after laser discharge) without obvious improvement in severity of stenosis. No angiographic loss of distal circulation was noted. To better define tissue- laser interactions in the live-rabbits, lasing of 15 totally occluded atherosclerotic rabbit arterial segments in vitro was done while the optical fiber was advanced or fixed. When the fiber was fixed, serial sections showed that the new lumen was flame shaped. The width and depth of the lumen increased with increasing laser energy. When the fiber was advanced, histologic examination showed a smooth cylindrical vascular channel with limited lateral tissue damage. This study demonstrated that lasers can recanalize atherosclerotic stenoses in a live animal preparation; however, arterial perforation remains a problem.

Animals↗

Inhibition of platelet function by injectable isosorbide dinitrate.

The possibility that isosorbide dinitrate (ISDN) inhibits platelet function in humans has been explored in vitro and in vivo. Incubation of citrated platelet-rich plasma from healthy subjects with scalar concentrations (1.25, 12.5 and 125 micrograms/ml) of ISDN for 5 and 10 minutes resulted in a decrease in platelet aggregation after ADP, adrenaline, and arachidonic acid at the highest drug concentration (mean decrease: 72% [p less than 0.01], 56% [p less than 0.05] and 62% [p less than 0.05], respectively, with the 10-minute incubation). Also, a significant reduction (30%) in generated thromboxane (TX)B2 levels was observed after arachidonic acid (p less than 0.01). ISDN was then infused at rate of 4 mg/hour for 30 minutes in 11 patients with angina and at a rate of 30 mg/hour for 20 minutes in 8. The smaller dose, which caused minor changes in arterial pressure and heart rate, was accompanied by a marked, significant decrease in ADP- and adrenaline-induced aggregation, with a nadir at 60 minutes from the infusion stop (decreases of 40% and 51% respectively). Circulating platelet aggregates also decreased, with a minimum (-41%, p less than 0.05) at the end of the infusion. The higher infusion rate, causing marked hemodynamic effects, was not accompanied by the occurrence of clear antiplatelet effects. Thus, ISDN can affect platelet function both in vitro and in vivo. The in vivo effect occurs at lower concentrations than in vitro but is blunted when a marked hemodynamic response occurs.

Adenosine Diphosphate↗

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation.

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF4), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGI2) (2 to 8 ng/kg/min) on PF4, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF4, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGI2 infusion resulted in a significant decrease of PF4 at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF4 levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF4 levels. The value of PF4 coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 +/- 28.9 vs 4.2 +/- 3.8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Failure of transdermal nitroglycerin to improve chronic stable angina: a randomized, placebo-controlled, double-blind, double crossover trial.

We assessed the effect of transdermal nitroglycerin (NTG-TTS), releasing 5 mg/24 hr, in 11 patients with chronic stable angina during a randomized, placebo-controlled, double-blind, double crossover trial of four 1-week periods. All patients had a positive exercise test and coronary artery disease prior to entry into the study. Efficacy was assessed weekly by anginal diaries, ambulatory ST segment recordings, and computerized exercise testing 2 to 4 hours after renewal of NTG-TTS. One patient withdrew in the first week (placebo) and was excluded from all analysis. The weekly frequency of anginal attacks was 9 +/- 11 (mean +/- SD) and 9 +/- 10 during the 2 placebo weeks and 11 +/- 14 and 9 +/- 11 during NTG-TTS; the time to 1 mm ST segment depression (seconds) was 268 +/- 178 and 303 +/- 217 with placebo and 228 +/- 221 and 285 +/- 178 with NTG-TTS; exercise duration (seconds) was 375 +/- 230 and 467 +/- 254 during placebo and was 394 +/- 233 and 412 +/- 236 during NTG-TTS. The weekly number of episodes of ST depression was 11 +/- 9 and 8 +/- 5 during placebo and 8 +/- 5 and 9 +/- 7 during NTG-TTS. Our study failed to show any consistent differences in patients treated with placebo or NTG-TTS.

Administration, Topical↗

alpha-Adrenergic receptors and coronary spasm: an elusive link.

In 14 consecutive patients with variant angina we investigated the possible role of coronary alpha-adrenergic receptors in the genesis of coronary spasm. In eight patients, computerized, beat-by-beat analysis of the electrocardiogram recorded during continuous Holter monitoring failed to reveal any increase of heart rate and corrected QT interval (both indexes of cardiac sympathetic activation) in the period preceding the onset of ST segment changes in 197 episodes of ischemia caused by coronary spasm. In the same patients, analysis of the circadian distribution of ischemic episodes revealed a significantly higher incidence in the early morning hours, when sympathetic activity is at the lowest level. Twelve patients underwent serial provocative testing with cold pressor, phenylephrine, or norepinephrine infusion and administration of ergonovine maleate. Ergonovine consistently reproduced coronary spasm in all 12 patients, while results of cold pressor testing were positive in only one. Infusion of phenylephrine (eight patients) or norepinephrine after beta-blockade (four patients) failed to precipitate myocardial ischemia. In five patients infusion of phentolamine at the highest tolerated dose did not reduce significantly the number of ischemic attacks when compared with placebo. In contrast to results of previous reports, our data seem to rule out the hypothesis that an increase of sympathetic outflow to the heart plays an important role in the genesis of coronary spasm. We cannot, however, exclude the possibility of localized alpha-stimulation of epicardial arteries.

Adult↗

Myocardial ischemia during ergonovine testing: different susceptibility to coronary vasoconstriction in patients with exertional and variant angina.

Coronary spasm is an accepted cause of transient myocardial ischemia in patients with variant angina; more recently it has been suggested that dynamic stenoses could also play an important role in the pathophysiology of exertional angina. To test this hypothesis we submitted 31 patients with histories typical of exertional angina to ergonovine testing and compared the electrocardiographic and clinical responses to those observed in seven patients with variant angina. All underwent bicycle ergometric exercise testing and coronary angiographic examination. For all tests, ST segment shifts of 0.1 mV or greater were considered to be diagnostic of myocardial ischemia. In patients with exertional angina, exercise testing produced diagnostic ST segment depression in 21 (68%). Ergonovine testing produced diagnostic ST segment depression in nine (29%). All nine had positive exercise test results and two- or three-vessel disease, yet the test was negative in seven other patients with positive exercise test results and similar angiographic findings. Conversely, in the seven patients with variant angina, results of exercise testing were positive in five (ST segment depression in two, ST elevation in three), while ergonovine produced ST segment elevation in all seven. Coronary angiographic examination showed normal arteries in two, one-vessel disease in four, and three-vessel disease in one. Results of all ergonovine tests were positive at values of rate pressure product much lower than those observed during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antiplatelet effects of isosorbide dinitrate in man.

Variable antiplatelet effects have been described for various antianginal drugs, including beta-blockers, verapamil, and nifedipine. To assess and characterize a possible similar effect of nitrates, platelet-rich plasma (PRP) from 22 healthy donors was incubated with scalar concentrations (1.25, 12.5, 125 micrograms/ml) of isosorbide dinitrate (ISDN) and with the vehicle alone for periods of 5 and 10 min. Platelet aggregation was successively induced by ADP (0.4-1.2 microM), adrenaline (0.8-8 microM), collagen (16.7 micrograms/ml), arachidonic acid (AA; 1 mM) and thrombin (0.5-2 U/ml). At the end of aggregation thromboxane (TX) B2 levels in PRP were assessed by RIA. A dose-dependent decrease in both platelet aggregation and TXB2 levels by all the inducers tested was demonstrated with both incubation times. Maximum inhibition of platelet aggregation was observed with ADP and adrenaline (72.0% and 55.6% respectively with 10-min incubation and the highest ISDN concentration. P less than 0.01 and P less than 0.05 respectively). A reduction in TXB2 levels in PRP was also observed, but reached statistical significance (P less than 0.01) only for AA-induced TXB2 generation. For an in vivo study ISDN was infused for periods of 30 min at 4 mg/h in 11 angina patients, and for periods of 20 min at 30 mg/h in an other eight, under ECG and arterial blood pressure monitoring. ADP- and adrenaline-induced aggregation and TXB2 production, and determination of circulating platelet aggregates (CPA) were performed in basal conditions and at 5, 15, 30 and 90 min from infusion start in the first group, at 5, 15, and 80 min in the second group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of intravenous prostacyclin in variant angina.

A lack in prostacyclin (PGI2) production due to atherosclerosis may play a role in the pathophysiology of some of the clinical manifestations of ischemic heart disease and in particular, of coronary vasospasm. We therefore evaluated the effects of i.v. PGI2 in nine patients with variant angina and six normal volunteers. In normal subjects, PGI2 (2.5, 5, 10 and 20 micrograms/kg/min) had significant antiplatelet effects, caused a dose-dependent decrease in both systolic and diastolic arterial pressure and a decrease in pulmonary resistance. Heart rate increased in a dose-dependent manner, but no consistent effects on myocardial contractility (evaluated by ultrasound) were observed. Side effects were negligible and readily reversible. Although producing obvious antiplatelet and vasodilatory effects, PGI2 did not affect the number, severity and duration of spontaneous ischemic episodes due to coronary vasospasm in five patients and ergonovine-induced spasm in three. However, the number of ischemic episodes was consistently reduced in one patient during four consecutive periods of PGI2 infusion alternated with placebo. a severe, prolonged ischemic episode with ST elevation and pain was consistently observed in this patient every time PGI2 was discontinued. In the appropriate environment, PGI2 can be administered safely to patients with ischemic heart disease. Occasionally, PGI2 may result in a complete disappearance of ischemic episodes due to coronary vasospasm, but usually it is ineffective. These conflicting results could be related to different etiologies of coronary spasm.

Adult↗

Failure of thromboxane A2 blockade to prevent attacks of vasospastic angina.

Thromboxane A2 (TxA2), released by aggregating platelets, has been proposed as a potential mediator of coronary vasospasm. We studied six patients with variant angina, a clinical syndrome due to coronary vasospasm, and one patient with frequent recurrent episodes of transient ST-segment depression at rest in whom the spasm was demonstrated angiographically. All patients underwent continuous ECG monitoring for 2 days before and 2 days after a single, low, i.v. dose of aspirin (2 mg/kg), which reduced TxB2 (the stable metabolite of TxA2) to less than 3% of the control values. There were 129 transient ischemic episodes during control and 146 after aspirin, when platelet TxB2 was reduced to negligible levels. The duration, severity and incidence of symptomatic episodes were not significantly affected by TxA2 blockade. We conclude that platelet TxA2 is probably not responsible for the initiation of coronary vasospasm.

Adult↗