Michael C. Petch

Aging-Associated Endothelial Dysfunction in Humans Is Reversed by L-Arginine *

OBJECTIVES This study investigated the hypothesis that aging selectively impairs endothelium-dependent function, which may be reversible by administration of L-arginine. BACKGROUND An impaired response to acetylcholine with aging has been demonstrated in humans. However, the mechanisms underlying this impaired response of the coronary microvasculature remain to be determined. METHODS We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate (GTN) and the endothelium-dependent vasodilator acetylcholine (1,3,10 and 30 micrograms/min) into the left coronary artery of 34 patients (27 to 73 years old) with atypical chest pain, negative exercise test results, completely normal findings on coronary angiography and no coronary risk factors. Coronary blood flow was measured with an intracoronary Doppler catheter. The papaverine and acetylcholine infusions were repeated in 14 patients (27 to 73 years old) after an intracoronary infusion of L-arginine (160 mumol/min for 20 min). RESULTS There was a significant negative correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation to papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17). The peak coronary blood flow response evoked by acetylcholine correlated significantly with aging before L-arginine infusion (r = -0.87, p < 0.0001), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). CONCLUSIONS The results suggest that aging selectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-arginine, a precursor of nitric oxide.

Early Complications After Dual Chamber Versus Single Chamber Pacemaker Implantation

This study was performed to compare the frequency of early complications after single chamber versus dual chamber permanent pacemaker implantation. Early complication was defined as one occurring in the 6‐week period following implantation. We prospectively analyzed consecutive pacemaker implantation from January 1987 to June 1993 at our regional center. All complications were also analyzed for the relationship to operator experience, the venous access route, and the presence of temporary pacing wire at the time of implantation of the permanent pacing system. A total of 2019 new pacemaker units were implanted during this period. 1733 patients (85.8%) received a VVI pacemaker and 286 (14.2%) a DDD unit. Wound infection occurredin 11 (0.6%) VVI patients and 6 (2.1%) DDD patients. Lead displacement occurred in 18(1 %) VVI patients and 15 (5.2%) DDD patients (11 [3.8%] atrial and 4 [1.4 %] ventricular). There were 10 (0.6%)pneumothoraces, 9 (0.5%) hematomas requiring drainage, 1 (0.06%) chylocele, and 2 (0.1%) deaths in the VVI group. There were 2 (0.7%) pneumothoraces, 2 (0.7%) hematomas, and no deaths in the DDD group. There was no significant increase in complications for experienced infrequent implanters (< 12 systems per year). In both groups the subclavian approach was associated with a risk of pneumothorax when compared to the cephalic approach. The rate of wound infection was higher in patients who had a temporary pacing wire in place. The use of prophylactic antibiotics does not appear to affect the incidence of wound infection. The early complications in the DDD group were higher than in the VVI group (8.7% vs 2.9%, P < 0.05), being mainly due to an increased incidence of wound infection and atrial lead displacement.

Late complications following permanent pacemaker implantation or elective unit replacement

Objective To determine the rate of late complications following first implantation or elective unit replacement of a permanent pacemaker system. Design Analysis of pacemaker data and complications prospectively acquired on a computerised database. Complications were studied over an 11 year period from January 1984 to December 1994. Setting Tertiary referral cardiothoracic centre. Patients Records of 2621 patients were analysed retrospectively. Main outcome measures Complications requiring repeat procedures occurring more than six weeks after pacemaker implantation or elective unit replacement. Results The overall rate of late complications was significantly lower after first implantation of a permanent pacemaker (34 cases, complication rate 1.4%, 95% confidence interval 0.9% to 1.9%) than after elective unit replacement (16 cases, complication rate 6.5% (3.3% to 9.7%). There were 20 cases of erosion, 18 infections, five electrode problems, and seven miscellaneous problems. Complications were more common with inexperienced operators (18.9% (6.0% to 31.8%)) than with experienced operators (0.9% (0.3% to 1.5%)). Conclusions The incidence of late complications following pacemaker implantation is low and compares favourably with early complication rates. The majority are caused by erosion and infection. Patients who have undergone elective unit replacement are at particular risk.

Effect of transcutaneous electrical nerve stimulation on coronary blood flow.

BackgroundAlthough neurostimulation has been shown to be of benefit in angina pectoris, the exact mechanism of its action is not clear. This study was performed to examine the effect of transcutaneous electrical nerve stimulation on coronary blood flow. Methods and ResultsThe effect of transcutaneous electrical nerve stimulation was studied in 34 syndrome X patients (group 1), 15 coronary artery disease patients (group 2), and 16 heart transplant patients (group 3). Coronary blood flow velocity (CBFV) in the left coronary system was measured at rest and after a 5-minute stimulation period with a Judkins Doppler. There was a significant increase in the resting CBFV in group 1 (from 6.8±4.1 to 10.5±5.7 cm/s, P < .001) and group 2 (from 6.8±4.1 to 10.5±5.7 cm/s, P < .001). However, there was no significant change in the resting CBFV in group 3. There were no significant changes in the coronary arterial diameters as a result of neurostimulation. There was a significant decrease in the epinephrine levels in group 1 (from 79.6±17.8 to 58.5±17.5 ng/L, P = .01) and group 2 (from 102.2±27.2 to 64.1 ± 19.1 ng/L, P = .01). ConclusionsTranscutaneous electrical nerve stimulation can increase resting coronary blood flow velocity. The findings suggest that the site of action is at the microcirculatory level and that the effects may be mediated by neural mechanisms.

Coronary angiography from the radial artery – experience, complications and limitations

AIMS to assess the outcomes, complications and limitations of coronary angiography performed via percutaneous radial artery puncture. METHODS AND RESULTS two hundred and fifty patients underwent diagnostic coronary angiography from the radial artery, 182 (72.8%) of whom had contraindications to the femoral approach, for example due to peripheral vascular disease (n=85), therapeutic anticoagulation (29), or failed femoral approach (17). Procedural success in this high-risk population was achieved in 231 patients (92.4%). Principle reasons for failure were unsuccessful radial access (5) and arterial spasm (5). Procedure duration (SD) for an operators first 20 cases compared with cases thereafter (min) was 47.7 (16.7) vs. 41.5 (14.6), P=0.0004; fluoroscopy time (min) 9.7 (7.1) vs. 6.6 (5.1), P=0.0001 and procedural success 89.6% vs. 94.1%, P=ns. Complications included two deaths associated temporally with catheterisation, three cases of arterial dissection without ischaemic sequelae and one transient ischaemic attack. CONCLUSIONS coronary angiography can be performed successfully from the radial artery, but this approach has limitations, which include the need to demonstrate dual palmar vascular supply, the prolonged learning phase, the procedural failure rate, patient discomfort and a demonstrable incidence of vascular and haemodynamic complications. We believe that radial coronary angiography should only be undertaken when there is a contraindication to the femoral approach.

Abnormal cardiac pain perception in syndrome X.

OBJECTIVES The purpose of this study was to determine whether a diminished cardiac pain threshold contributes to chest pain in patients with syndrome X. BACKGROUND There have been some reports of an altered pain perception in syndrome X. METHODS Intracardiac catheter manipulation was performed in four groups of patients (syndrome X [group 1, 36 patients]; mitral valve disease and normal coronary arteries [group 2, 36 patients]; mitral valve disease and coronary artery disease [group 3, 36 patients]; and heart transplant recipients with normal coronary arteries [group 4, 36 patients]). Coronary flow velocity was measured in patients with syndrome X and in transplant recipients by use of an intracoronary Doppler catheter positioned in the left anterior descending coronary artery at intracardiac catheter manipulation. Coronary flow reserve in response to papaverine was also measured in patients with syndrome X and in transplant recipients. RESULTS Intracardiac stimulation produced typical anginal chest pain in 34 group 1 (syndrome X) patients (94%). However, chest pain was produced only in five patients (14%) in group 2, seven patients (19%) in group 3 and no patients in group 4. There were no significant changes in coronary blood flow velocity associated with chest pain in group 1 patients. Coronary flow reserve in response to a hyperemic dose of intracoronary papaverine was significantly lower in the syndrome X group. There was no significant difference in the prevalence with which the stimulation tests produced chest pain in patients with syndrome X with an impaired coronary flow reserve or a positive radionuclide scan. CONCLUSIONS The results of our study suggest that abnormal cardiac pain perception is a fundamental abnormality in syndrome X.

Coronary angiography in the fully anticoagulated patient: The transradial route is successful and safe

The radial approach to coronary angiography is intuitively attractive for fully anticoagulated patients (INR > 2) but no data exist concerning efficacy or safety of this procedure. The consensus view is that the femoral approach is contraindicated in fully anticoagulated patients, and though some operators undertake femoral catheterization in such patients and use closure devices, there are no data to suggest that it is safe to do so. At our institution, the radial approach for coronary angiography is reserved for patients in whom there is a relative contraindication to the femoral route. We have undertaken over 600 radial coronary angiograms in such patients since 1996, 66 of whom underwent transradial catheterization specifically because of anticoagulation status (INR > 2). Thirty‐eight patients (58%) were male, average age 67 ± 11 years. All 66 patients had an INR > 2 but < 4.5. The approach was left radial in 26 (39%), right radial in the remainder; sheath size was 4 Fr in 4 (6%), 5 Fr in 13 (20%), and 6 Fr in 49 (74%). Seven operators in total were involved, though two operators undertook the majority of cases (47; 71%). Success rate was 97%, with no failure of access, and only one minor postprocedural hemorrhage. Failures were due to radial artery atherosclerosis (1) and subclavian tortuosity (1). The radial approach to coronary angiography is safe and to be recommended in the fully anticoagulated patient. Cathet Cardiovasc Intervent 2003;58:8–10.

Radial Versus Femoral Approach for Diagnostic Coronary Angiography in Stable Angina Pectoris

We compared coronary angiography of the radial artery using 6Fr catheters in 116 patients with that of the femoral artery in 100 case controls. We showed that transradial coronary angiography offers a useful alternative to the femoral route and can be performed without resorting to 5Fr catheters.

Transradial coronary angiography in patients with contraindications to the femoral approach: An analysis of 500 cases

The transradial approach to coronary angiography is considered by some to be a route of choice, by others to be a route that should be used only where there are relative contraindications to the femoral approach. We present the largest series to date of patients in whom transradial coronary angiography was undertaken specifically because of contraindications to the femoral approach. Since 1995, patients at this cardiothoracic center have been considered for a transradial approach to coronary angiography if there were relative contraindications to the femoral route. Data from 500 patients was prospectively collected. Patients were aged 66 ± 9 years; 72% were male. Indications for the radial approach included peripheral vascular disease (305), therapeutic anticoagulation (77), musculoskeletal (59), and morbid obesity (32). Sixty‐eight patients (14%) required a radial procedure following a failed femoral approach. Access was right radial 291 (58%), left radial 209 (42%). Eighteen operators were involved, but two operators undertook 355 (71%) of the cases. Catheter gauge was 6 Fr (n = 243; 49%), 5 Fr (219; 43%), and 4 Fr (29; 6%). The procedure was successful in 463 cases [92.6%; 88.2% for nonmajority vs. 94.4% (P < 0.05) for the two majority operators]. Success in males (93.6%) significantly exceeded that in females (90.1%; P < 0.05). In‐catheter‐laboratory duration was 45 ± 17 min; fluoroscopy time, 7.5 ± 6 min; radiation dose, 40 ± 23 CGy. The procedure was without incident in 408 cases (82%). There were procedural difficulties in 18% of cases, including radial artery spasm (12%) and vasovagal response (5%). The incidence was higher with 6 Fr catheters (23%) than with 5/4 Fr (15%; P < 0.05). Major procedural complications occurred in three cases: brachial artery dissection in one and cardiac arrest in two. Postprocedure major vascular complications numbered three: claudicant pain on handgrip in one, ischemic index finger (with subsequent terminal phalanx amputation due to osteomyelitis) in one, and ischemic hand for 4 hr in one. Patients with contraindications to the femoral approach form a high‐risk group. In these patients, transradial cardiac catheterization can be performed successfully and with a low risk of major complications. Minor adverse features remain frequent, occurring in one in five cases, though difficulties are minimized both with increasing operator experience and smaller sheath diameter. Catheter Cardiovasc Interv 2004;61:60–66.

Is coronary flow reserve in response to papaverine really normal in syndrome X

BACKGROUND An impaired coronary flow reserve in syndrome X has been demonstrated by many studies. Recently, however, a normal coronary flow reserve in response to papaverine was reported, but the number of patients in these studies was small. The aim of this study was to investigate whether coronary flow reserve in response to intracoronary papaverine is really impaired in syndrome X. METHODS AND RESULTS We investigated 53 syndrome X patients (typical angina, a positive exercise test, and completely normal coronary arteries on angiography) and 26 heart transplant patients with normal coronary arteries (control group). All antianginal medications were stopped 48 hours before the study. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery and was connected to a Millar velocimeter. The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured. Coronary flow reserve was defined as the ratio of hyperemic coronary blood flow velocity in response to papaverine and resting coronary blood flow velocity. The coronary flow reserve (mean +/- SD) in the syndrome X group was 2.72 +/- 1.39. The coronary flow reserve in the control group was significantly higher at 5.22 +/- 1.26 (P < .01). In both groups there was no significant difference in the heart rate or the mean arterial pressure during the study. CONCLUSIONS Our study shows that coronary flow reserve in response to intracoronary papaverine is impaired in syndrome X patients.