Infectious complications related to the use of the angio-seal hemostatic puncture closure device.
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
M Haude
Publications and source records attributed to M Haude.
Potential embolization by atherosclerotic debris dislodged from aortic wall during cardiac catheterization:: histological and clinical findings in 7,621 patients.
Embolic events during cardiac catheterization have been attributed to atherosclerotic aortic debris dislodged by catheter manipulation. We evaluated the frequency and the histologic morphology of atherothrombotic material retrieved during placement of coronary catheters in patients undergoing diagnostic or interventional cardiac procedures. Over a 4-year period, macroscopically visible aortic debris from coronary catheters, if present after advancement to the ascending aorta, was obtained for histologic examination. In 41 of 7,621 patients (0.54%), visible atherothrombotic material was present in the backflow of catheters. Debris occurred most frequently with 8 Fr guiding catheters (98%). Histologic examination showed foam cells, cholesterol crystals, and amorphic lipoid substance as markers of atheromatous material from atherosclerotic plaques in 38/41 patients (93%) with former plaque hemorrhage in 55% of them. In three patients, fresh thrombus material was observed (7%). None of these patients showed in-hospital ischemic complications. Although visible atheromatous material is a rare phenomenon in cardiac catheterization, an increased risk of scraping debris is associated with large-lumen guiding catheters. In order to avoid vascular embolization, the use of smaller guiding catheters and sufficient free backflow of catheters after advancement are recommended.
Adult↗
A word of caution on unrestricted use of synthetic stent grafts in native coronary arteries
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Journal Article↗
Nonsurgical retrieval of embolized coronary stents.
Embolization of coronary stents before deployment is a rare but challenging complication of coronary stenting. Different methods for nonsurgical stent retrieval have been suggested. There were 20 cases (0.90%) of intracoronary stent embolization among 2,211 patients who underwent implantation of 4,066 stents. Twelve of 1,147 manually crimped stents (1.04%) and eight of 2,919 premounted stents were lost (0.27%, P < 0.01) during retraction of the delivery system, because the target lesion could not be either reached or crossed. Percutaneous retrieval was successfully carried out in 10 of 14 patients (71%) in whom retrieval was attempted. In 10 patients, stent retrieval was tried with 1.5-mm low-profile angioplasty balloon catheters (success in 7/10) and in seven cases with myocardial biopsy forceps or a gooseneck snare (success in 3/7). Three patients (15%) underwent urgent coronary artery bypass surgery after failed percutaneous retrieval, but their outcomes were fatal. In two patients, stents were compressed against the vessel wall by another stent, without compromising coronary blood flow. In two patients, a stent was lost to the periphery without clinical side effects; treatment was conservative in these cases. Embolization of stents before deployment is a rare but serious complication of coronary stenting, with hazardous potential for the patient. Manual mounting of stents is associated with a significantly higher risk of stent embolization. Stent retrieval from the coronary circulation with low-profile angioplasty balloon catheters is a readily available and technically familiar approach that has a relatively high success rate.
Aged↗
Percutaneous transluminal laser guide wire recanalization of chronic subclavian artery occlusion in symptomatic coronary-subclavian steal syndrome.
Treatment of subclavian artery stenosis by percutaneous balloon angioplasty and adjunctive stent placement was shown to be safe and efficacious, but it may be limited in tight stenoses and long occlusions. We describe the case of a patient who experienced progressive angina pectoris associated with signs of cerebrovertebral insufficiency 9 yr after bypass surgery, including left internal mammary artery (LIMA) grafting to the left anterior descending coronary artery. Angiography showed reversed flow through the LIMA graft into the subclavian artery and a 4-cm occlusion beginning at the origin of the left subclavian artery, representing a rare coronary-subclavian steal syndrome. After a conventional approach failed, recanalization was performed successfully using laser guide wire angioplasty with adjunctive stent placement in a combined radial and femoral approach.
Angioplasty, Balloon, Laser-Assisted↗
[Electromechanically controlled versus roengenologically guided percutaneous transluminal laser myocardial revascularization].
Transmyocardial laser revascularization is a modern therapeutic concept for patients with end-stage coronary artery disease not eligible for bypass surgery, percutaneous coronary interventions or heart transplantation. Although the principal idea of creating additional myocardial perfusion from the cavum of the left ventricle was derived from observations in reptile hearts, histological investigations suggest that channel patency is not the underlying mechanism for improved clinical symptoms. Sympathetic denervation and angioneogenesis may be additional explanations for improvement of angina and stress tolerance. The first experiences with transmyocardial laser revascularization were made using a surgical approach. Two randomized multicenter trials could show a significant improvement in angina and stress tolerance 12 months after creating channels using laser technique. While these results were obtained by performing thoracotomy, catheter-based systems have been designed for a less invasive approach of this technique. A further advantage of these new systems is that regions like the septum can be treated which are not eligible for a surgical approach. Using percutaneous transluminal catheter-based systems channels of up to 6 mm length can be created. Beside the fluoroscopic guided creation of myocardial channels a new mapping system has been applied using electromechanical features of viable myocardial tissue. This system is based on the observation that endocardial electrograms recorded from an infarcted area are characterized by very low amplitude and fractionated morphology. This system allows online mapping of viable myocardium and provides spatial, electrical, and mechanical information of the myocardium. This method of electromechanical mapping highly correlates with results obtained from myocardial perfusion scans. Recent preliminary clinical trials demonstrated that catheter-based creation of myocardial channels is a feasible and successful alternative to the surgical laser revascularization. Also with this approach a significant improvement in angina and stress tolerance can be achieved. The results of the PACIFIC study, the first randomized multicenter study using percutaneous transluminal laser revascularization, demonstrates that after 3 and 6 months more than half of the patients presented improved angina of at least 1 Canadian-Cardiovascular-Society class. Whether electromechanical guided myocardial laser revascularization is more efficient than fluoroscopic guided has not been proven yet. Further studies will have to evaluate this issue.
Animals↗
[Transluminal exclusion of a subclavian artery aneurysm with stent-graft implantation].
In a 73 year-old male patient with generalized atherosclerosis, known infrarenal abdominal aortic aneurysm, renal artery stenosis, and coronary artery disease, an aneurysm of the proximal left subclavian artery was successfully excluded by implantation of a JOSTENT-Peripheral stent graft. Angiographic follow up after 6 and 12 months showed an excellent outcome with complete exclusion of the aneurysm. Intravascular ultrasound showed no neo-intimal hyperplasia within the stent. A computed tomography revealed complete thrombosis of the aneurysm.
Aged↗
[Biophysical study of coronary stents: which factors influence the dilatation and recoil behavior?].
In Europe more than fifty stents are currently available for the therapy of coronary artery disease. Nonetheless it is unknown whether material and design influence the stent's behavior. We have studied the recoil and dilatation behavior of five currently available stainless steel (316L) stents compared to stent prototypes made of pure titanium. Furthermore we have investigated how the behavior is influenced by the process of crimping. The aim of this work was to determine material and design characteristics, which influence the recoil and dilatation behavior. The 316L stents showed a homogeneous behavior (plateau pressure min. 1.15 +/- 0.01 atm, max. 0.26 +/- 0.03 atm, recoil min. 0.15 +/- 0.03%, max. 0.26 +/- 0.03%). The titanium stent showed a linear response to the balloon expansion. This was seen in a significantly lower plateau pressure (0.43 +/- 0.15 atm, p < 0.001). Despite the material characteristics of titanium, there were no significant differences in the recoil behavior (0.28 +/- 0.02%). Crimping leads to stent alterations which result in a significantly higher plateau pressure (1.9 +/- 0.07 atm vs. 2.7 +/- 0.58 atm, p < 0.001) and a reduced end-diameter (3.6 +/- 0.02 mm vs. 3.54 +/- 0.05 mm, p < 0.005). The presented data show that the dilatation behavior is relying on the stent material while the recoil is strongly influenced by the stent design.
Angioplasty, Balloon, Coronary↗
X-ray densitometry for the measurement of regional myocardial perfusion.
The evaluation of regional myocardial blood flow (RMBF) during cardiac catheterization is of particular diagnostic interest. The purpose of this investigation was to validate x-ray densitometric parameters for the evaluation of RMBF. In five anesthetized dogs, arterial flow in the circumflex coronary artery was measured continuously with an electromagnetic flowmeter, and RMBF was determined by colored microspheres. Five different perfusion levels were created by mechanical obstruction of the coronary artery or by intravenous infusion of adenosine. At each steady-state perfusion level, digital subtraction coronary angiograms were obtained for densitometric analysis. Results documented a close correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 = 0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between 0.36 ml/(min x g) and 11.16 ml/(min x g). Maximum myocardial contrast density (Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and, therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT) showed no correlation to RMBF (r2 = 0.017). Repeat densitometric measurements for different perfusion levels revealed a good reproducibility for MTT (accuracy: 0.001 s; precision: 0.447 s or 6.7 %) and RT (accuracy: 0.014 s; precision: 0.202 s or 10.4 %), while AT (accuracy: 0.072 s; precision: 0.420 s or 68.5%) and Imax (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation. Myocardial perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 = 0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2 = 0.04). In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a close correlation to RMBF. Therefore, only these parameters can be recommended for calculations of RMBF and its reserve under clinical conditions.
Absorptiometry, Photon↗
Corrected coronary flow velocity reserve: a new concept for assessing coronary perfusion.
OBJECTIVES: In order to limit the variability of coronary flow velocity reserve (CFVR), we analyzed which factors independently affect CFVR and established a new parameter integrating these factors. BACKGROUND: Coronary flow velocity reserve (CFVR) is a frequently used parameter for evaluating the physiological significance of epicardial stenosis and microvascular function. Since CFVR measurements are done in substantially different hemodynamic and clinical situations, interpretation of CFVR requires correction for major influencing factors. METHODS: In 141 patients with angina-like symptoms and angiographically unobstructed coronary arteries, intracoronary Doppler measurements were performed in at least two coronary vessels. Coronary flow velocity reserve was calculated as the ratio of hyperemic average peak velocity (hAPV), after intracoronary bolus of adenosine, to baseline average peak velocity (bAPV). RESULTS: Analysis of covariance revealed that only bAPV (p < 0.0001) and age (p < 0.0001) were independent factors influencing CFVR. Based on a regression model for estimation of predicted CFVR values, individual CFVR values (CFVRind) obtained at different bAPV and age were transformed in corrected CFVR values (CFVRcorr) by relating them to a mean bAPV of 15 cm/s and a mean age of 55 years. The transformation from CFVRind into CFVRcorr for the left anterior descending artery can be done by using the following equation: CFVRcorr = 2.85*CFVR(ind)*10(0.48*log(bAPV)+(0.0025*age)-1.16). When applying this new parameter to conditions assumed to cause microvascular dysfunction, analysis showed that only patients with diabetes showed a significant decrease of traditional CFVR and CFVRcorr, whereas a history of hypertension and current smoking habit had no influence on CFVRcorr. CONCLUSIONS: The concept of CFVRcorr standardizes CFVR for bAPV and age as the major physiological determinants. Especially in patients with microvascular dysfunction, this approach may help to discriminate between conditions directly affecting vasodilator reserve and conditions primarily affecting bAPV.
Blood Flow Velocity↗
Dose-dependent effects of intracoronary verapamil on systemic and coronary hemodynamics.
Calcium antagonists are used in interventional cardiology to prevent coronary vasoconstriction or to overcome the no-reflow phenomenon. The aim of the current study was to evaluate the dose-dependent effects of intracoronary verapamil on systemic and coronary hemodynamics. In 20 patients scheduled for routine coronary angiography, heart rate, blood pressure, and ECG recordings were recorded continuously and intracoronary flow velocity was obtained by intracoronary Doppler measurements in angiographically normal vessels. The cross-sectional area, measured by quantitative coronary angiography, allowed the calculation of coronary blood flow (CBF) and the coronary vascular resistance index (CVRI). Without premedication, increasing dosages of verapamil (0.01 mg, 0.1 mg, 1.0 mg, and 2.0 mg) were injected into the left coronary artery. Intracoronary verapamil administration led to a decrease in systemic blood pressure only after administration of 1.0 mg or 2.0 mg (change in mean arterial pressure: from 87.6 +/-14.6 mmHg to 80.1 +/- 14.9 mmHg and 78.5 +/- 13.9 mmHg, respectively; both P < 0.05) without a change in heart rate. Epicardial diameters of the left coronary artery increased only at dosages of 1.0 mg and 2.0 mg (from 2.14 +/- 0.4 mm to 2.22 +/- 0.3 mm, P < 0.01), whereas the coronary blood flow velocity increased significantly at the smallest dosage of 0.01 mg (from 19.9 +/- 8.7 cm/s to 33.2 +/- 14.9 cm/s, P < 0.001) and was further enhanced with increasing dosages. CBF increased and CVRI decreased at every dosage of verapamil compared with baseline values. CBF increased also after 0.1 mg (from 13.5 +/- 6.5 mL/min to 19.5 +/- 9.3 mL/min; P < 0.05), reaching a maximal effect after administration of 1.0 mg verapamil (26.3 +/- 16.1 mL/min, P < 0.05). Application of 2.0 mg did not further increase CBF compared with 1.0 mg. Intracoronary application of verapamil leads to a decrease in systemic blood pressure at higher dosages, whereas heart rate remains unchanged at any dosage. The maximal increase in coronary blood flow and decrease in vascular resistance can be reached by administration of 1.0 mg verapamil into the left coronary artery.
Adult↗
Angiographical and Doppler flow-derived parameters for assessment of coronary lesion severity and its relation to the result of exercise electrocardiography. DEBATE study group. Doppler Endpoints Balloon Angioplasty Trial Europe.
AIMS: Evaluation of angiographical and intracoronary Doppler-derived parameters of coronary stenosis severity. METHODS AND RESULTS: A total of 225 patients with one-vessel disease were studied before PTCA and at 6 months follow-up. Exercise electrocardiography was performed to document presence (n = 157) or absence (n = 138) of an ST segment shift (> or =0.1 mV). Intracoronary blood flow velocity analysis was performed to determine the proximal/distal flow velocity ratio, the distal diastolic/systolic flow velocity ratio and coronary flow velocity reserve. Receiver operator characteristic curves were calculated to assess the predictive value of these variables compared with the exercise test. The distal coronary flow velocity reserve demonstrated the best linear correlation for both percentage diameter stenosis and minimum lumen diameter (r = 0.67 and r = 0.66; P<0.01), compared to the diastolic/systolic flow velocity ratio (r = 0.19 and r = 0.14; P<0.01) and the proximal/distal flow velocity ratio (r = 0.03 and r = 0.07; not significant). The areas under the curve were 0. 84+/-0.02; 0.82+/-0.03 and 0.83+/-0.03 for diameter stenosis, minimum lumen diameter and coronary flow velocity reserve, respectively. Logistic regression analysis revealed that the percentage diameter stenosis or minimum lumen diameter and coronary flow velocity reserve were independent predictors for the result of stress testing. CONCLUSIONS: The distal coronary flow velocity reserve is the best intracoronary Doppler parameter for evaluation of coronary narrowings. Angiographical estimates of coronary lesion severity and distal coronary flow velocity reserve are good and independent predictors for the assessment of functional severity of coronary stenosis, emphasizing the complementary role of these parameters for clinical decision making.
Adult↗
A randomized comparison of balloon angioplasty versus rotational atherectomy in complex coronary lesions (COBRA study).
AIMS: Rotablation is a widely used technique for the treatment of complex coronary artery lesions but is so far only poorly supported by controlled studies. The Comparison of Balloon-Angioplasty versus Rotational Atherectomy study (COBRA) is a multicentre, prospective, randomized trial to compare short- and long-term effects of percutaneous transluminal coronary angioplasty (PTCA) and rotablation in patients with angiographically pre-defined complex coronary artery lesions. METHODS AND RESULTS: At seven clinical sites 502 patients with pre-defined complex coronary artery lesions were assigned to either PTCA (n=250) or rotablation (n=252). Primary end-points were procedural success, 6-month restenosis rates in the treated segments, and major cardiac events during follow-up. Procedural success was achieved in 78% (PTCA), and 85% (rotablation) (P=0.038) of cases. Crossover from PTCA to rotablation was 4% and 10% vice versa (P=0.019). There was no difference between PTCA and rotablation with respect to procedure-related complications such as Q wave infarctions (2.4% each), emergency bypass surgery (1.2% versus 2.4%), and death (1.6% versus 0.4%). However, more stents were required after PTCA (14.9% versus 6.4%, P<0.002), predominantly for bailout or unsatisfactory results. Including bail-out stents as an end-point, the procedural success rates were 73% for angioplasty and 84% for rotablation (P=0.006). At 6 months, symptomatic outcome, target vessel reinterventions and restenosis rates (PTCA 51% versus rotablation 49%, P=0.33) were not different. CONCLUSION: Complex coronary artery lesions can be treated with a high level of success and low complication rates either by PTCA with adjunctive stenting or rotablation. The long-term clinical and angiographic outcome is comparable.
Adult↗
Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial.
AIMS: A randomized trial was performed to assess the safety and efficacy of a laser guidewire, in the treatment of chronic coronary occlusions. METHODS AND RESULTS: In 18 European centres, 303 patients with a chronic coronary occlusion were randomized to treatment with either the laser guidewire (n=144) or conventional guidewires (mechanical guidewire, n=159). The primary end-point of the study was treatment success, defined as reaching the true lumen distal to the occlusion by the allocated wire within 30 min of fluoroscopic time: laser guidewire vs mechanical guidewire; 52.8% (n=76) vs 47.2% (n=75), P=0.33. Serious adverse events following the initial guidewire attempt were 0% (laser guidewire) and 0.6% (mechanical guidewire), respectively. Angioplasty (performed following successful guidewire crossing) was successful in 179 patients (91%, laser guidewire n=79, mechanical guidewire n=100), followed by stent implantation in 149 (79%). At the 6-month angiographic follow-up, the difference in binary restenosis rate (laser guidewire vs mechanical guidewire; 45.5% vs 38.3 %, P=0.72) or reocclusion rate (25.8% vs 16.1%, P=0.15) did not reach statistical significance. At 1, 6 and 12 months, angina and event-free survival were 69%, 35% and 24% (laser guidewire) vs 74%, 40% and 31% (mechanical guidewire). CONCLUSION: Although laser guidewire technology was safe, the increase in crossing success did not reach statistical significance.
Aged↗
Safety of intracoronary Doppler flow measurement.
BACKGROUND: With the introduction of Doppler-tipped guide wires, intracoronary Doppler flow measurement has been increasingly accepted as an additional diagnostic approach in the catheterization laboratory. However, the safety of intracoronary Doppler flow measurement has not been well-investigated. The purpose of our study was to evaluate the safety of intracoronary Doppler flow measurement using the Doppler FloWire (Cardiometrics, Mountain View, Calif). METHODS AND RESULTS: A total of 906 patients were examined by intracoronary Doppler with a 0.014-inch or an 0.018-inch Doppler FloWire. For coronary flow reserve measurement, intracoronary injection of adenosine or papaverine was used. Of the patients studied, 77 were cardiac transplant recipients and 829 were patients who had not received a transplant, of whom 617 had undergone diagnostic coronary procedures and 212 had coronary interventions. In 27 (2.98%) of 906 patients adverse cardiac events were observed. Fifteen (1.66%) of 906 patients had severe transient bradycardia develop (asystole or second- to third-degree atrioventricular block) after intracoronary administration of adenosine, 14 of which occurred in the right coronary artery and 1 in the left anterior descending artery. Nine (0.99%) of 906 patients had coronary spasm during the passage of the Doppler wire (5 in the right coronary artery, 4 in the left anterior descending artery). Two (0.22%) of 906 patients had ventricular fibrillation during the procedure. Hypotension with bradycardia and ventricular extrasystole each occurred in 1 (0.11%) of 906 patients. The incidence of complication was significantly higher in transplant recipients than in patients who underwent either diagnostic or interventional procedures (12.99% vs 2.43% vs 0.94%, P <.001). The Doppler measurements in the right coronary artery were associated with a higher incidence of complications, especially bradycardia, compared with the left anterior descending and the left circumflex arteries (right coronary, 5.87% vs left anterior descending, 1.05% vs left circumflex, 0.17%; P <.001). All complications were cured medically. CONCLUSION: Intracoronary Doppler flow measurement with Doppler wires and intracoronary administration of adenosine is a safe method. However, severe complications such as bradycardia and coronary spasm can occur. Attention should be paid to the examination of the right coronary artery, especially in heart transplant recipients.
Adenosine↗
Immediate stent implantation versus conventional techniques for the treatment of abrupt vessel closure or symptomatic dissections after coronary balloon angioplasty.
BACKGROUND: Coronary stenting was initially designed to treat a bailout scenario. Prospective randomized trials comparing stent implantation with standard techniques, including emergency coronary artery bypass grafting, are lacking. The aim of this trial was to test the superiority of immediate stent implantation compared with standard techniques for the treatment of abrupt or threatening closure after coronary balloon angioplasty. METHODS: In a prospective trial, 100 patients with abrupt vessel closure or symptomatic dissections causing objective signs of ischemia were randomly assigned to treatment with immediate placement of stents (n = 51) versus standard techniques such as prolonged dilatation or emergency bypass surgery (n = 49). The primary end point was the achievement of successful stabilization not requiring crossover to the other study group. Secondary end points included event-free survival and restenosis. RESULTS: Successful stabilization was achieved in 94% of patients in the stent group compared with 78% of patients in the standard treatment group (P =.038). Two patients died in each group, and there was a trend toward a higher incidence of myocardial infarction (16% vs 8%; P =.163) and a significantly increased creatine phosphokinase level (245 IU/L [95% confidence interval, 217-265 IU/L] vs 179 IU/L [confidence interval 140-212 IU/L]; P =.0002) in the standard treatment group. Event-free survival after 250 days was 72% in the stent group compared with 29% in the standard treatment group (P =.001). The angiographic restenosis rate was 30% in the stent group versus 59% in the standard treatment group (P =.01). CONCLUSIONS: Immediate stenting, if technically feasible, shows superior short- and long-term results compared with standard treatment options.
Aged↗
Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo.
OBJECTIVE: To identify any potential relations between the size of an emptied plaque cavity and the remodelling pattern, plaque or vessel dimensions, lumen narrowing, and other ultrasonic lesion characteristics. DESIGN: Intravascular ultrasound was used to examine prospectively 51 ruptured ulcerated coronary plaques. Cross sectional area measurements comprised lumen, vessel, plaque, and emptied plaque cavity. Lumen narrowing was calculated as 1 - (lesion lumen area/reference lumen area) x 100%. A remodelling index was calculated as lesion vessel area/reference vessel area, and plaques were divided into those with values > 1.05 (group A) and </= 1.05 (group B). RESULTS: Of the total of 51 plaques, 36 (71%) were assigned to group A and 15 (29%) to group B. In neither group was there a significant difference in reference dimensions and lumen narrowing. However, lesion vessel (mean (SD): 22.6 (8.1) mm(2) v 17. 5 (4.3) mm(2); p = 0.006) and plaque areas (15.8 (6.2) mm(2) v 12.8 (3.2) mm(2); p = 0.03) were greater in group A than in group B. The cavity inside the plaque was larger in group A than in group B (2.8 (1.6) mm(2) v 1.8 (0.9) mm(2); p = 0.007) and showed a positive linear relation with lesion and reference vessel size (r = 0.58 and 0.56, respectively; p < 0.001), but not with lumen narrowing. CONCLUSIONS: The size of the emptied cavity inside ruptured plaques is on average larger in lesions with adaptive vascular remodelling, and shows a linear relation with lesion plaque and vessel size and with the reference dimensions, but not with the degree of lumen narrowing.
Adult↗
G protein beta3 subunit 825T allele and enhanced coronary vasoconstriction on alpha(2)-adrenoceptor activation.
Recently, alpha(2)-adrenoceptor activation was shown to play an important role in the vasoconstriction of normal coronary arteries, whereas in the presence of atherosclerosis, the activation of both alpha(1)- and alpha(2)-adrenoceptors reduces coronary blood flow in humans. alpha(2)-Adrenoceptors activate pertussis toxin (PTX)-sensitive G proteins, whereas alpha(1)-adrenoceptors couple to PTX-insensitive G proteins. Thus, the 825T allele of the beta3 subunit of heterotrimeric G proteins, associated with enhanced PTX-sensitive G protein signaling, was expected to determine the alpha(2)-adrenoceptor-, but not the alpha(1)-adrenoceptor-, mediated reduction in coronary blood flow (CBF). Genotyping was performed on 48 individuals. Twelve of the 48 received the alpha(1)-adrenoceptor agonist methoxamine (MTX; 5 mg IC), and 12 received the alpha(2)-adrenoceptor agonist BHT 933 (BHT; 5 mg IC). Twenty-four additional individuals received both MTX and BHT during the same investigational procedure. CBF was calculated on the basis of coronary angiography and intracoronary Doppler flow velocity measurement. Drug-related ischemia was assessed on the basis of ST-segment changes and angina pectoris. In response to BHT, but not to MTX, CBF was reduced to a significantly greater extent in 825T allele carriers (58+/-4%, n=16) than in individuals homozygous for the C825 allele (28+/-4%, n=19, P=0.001). This finding was independent of cholesterol levels, mean arterial blood pressure, and the presence or absence of coronary artery disease. Ischemic events in response to BHT occurred more frequently in 825T allele carriers than in homozygous 825C allele carriers (P=0.01). alpha(2)-Adrenoceptor coronary vasoconstriction is genetically determined and significantly enhanced in GNB3 825T allele carriers.
Adrenergic alpha-Agonists↗