Beta-receptor mechanisms in the superficial limb veins of the dog.

The lateral saphenous vein of dogs was perfused at constant flow with autologous arterial blood, and perfusion and femoral vein pressures were monitored; changes in the difference between these pressures were due to changes in venomotor activity. Injection of isoproterenol into the perfusate caused the vein to dilate. The amount of dilatation depended on smooth muscle tension in the wall of the vein before injection. When this was minimal (after sympathectomy), isoproterenol had no effect. During venoconstriction produced by electrical stimulation of the lumbar sympathetic chain or by the infusion of venoconstrictor drugs, the dilating action of 0.1 mg of isoproterenol was measured. Expressed as a percentage of the initial constriction caused by sympathetic stimulation, 5-hydroxytryptamine, or 1 M potassium chloride, the extent of the dilatation was 86.7+/-4.3 (SE of mean), 79.7+/-4.2, and 87.7+/-3.2, respectively. With norepinephrine and epinephrine infusions, the isoproterenol dilatations were less (65.1+/-9.0 and 55.2+/-7.2, respectively), consistent with the stimulant action of these agents on both alpha and beta receptors; such action was confirmed by comparing the responses to nerve stimulation and infusions of norepinephrine and epinephrine before and after betareceptor blockade. The venoconstriction caused by sympathetic stimulation and by infusions of norepinephrine and epinephrine was greatly enhanced by cooling the vein (decreasing perfusate temperature), but the dilating action of isoproterenol appeared to be insensitive to changes in temperature. The data suggest that beta receptors are specific entities and, when maximally stimulated, are capable of causing a venous relaxation that is proportional to the initial degree of tension in the vein wall.

Therapeutic defibrination and heparin therapy in the prevention and resolution of experimental venous thrombosis.

The application of phenol to the femoral veins of anesthetized dogs resulted in an occluding thrombus in 24 of 25 veins at 1 week. Serial venography and eventual histology showed that these veins remained occluded over a 5-week observation period, the thrombi undergoing organization. Therapeutic defibrination was achieved with administration of an enzyme from venom of the pit viper (Arvin). Arvin, administered for 1 week immediately following phenol application and before thrombus formation had occurred, prevented thrombosis in all 10 such veins, and serial venography for a further 4 weeks showed that the veins remained patent. Administration of Arvin was begun 24 hours postoperatively, when venography had demonstrated an occluding thrombus and failed to clear any of 11 veins after 3 weeks of treatment. Intravenous administration of heparin, 10,000 units, at 6, 6, and 12-hour intervals in a 24-hour period, was begun immediately after phenol application and continued for 1 week; 10 of 12 veins were blocked at 1 week. Following the same dose of heparin every 6 hours four of eight veins were blocked at 1 week. The results indicate that when the vascular endothelium is damaged, therapeutic defibrination is more effective than heparin therapy in preventing venous thrombosis. Arvin therapy has no significant thrombolytic effect even if the thrombus is less than 24 hours old.

Primary restrictive cardiomyopathy: clinical and pathologic characteristics.

Twenty-four patients with restrictive cardiomyopathy were identified at St. Thomas' Hospital during a 17-year period. All had endomyocardial biopsy, but in two patients the biopsy specimens were small and nondiagnostic. Seven patients had amyloidosis and five had other specific heart muscle diseases. The remaining 10 patients with primary restrictive cardiomyopathy had myocyte hypertrophy or interstitial fibrosis, or both. Patients with primary restrictive cardiomyopathy presented earlier but survived longer after presentation than did those with amyloidosis. In each group, survival after cardiac catheterization was related to cardiac index but not to filling pressures. Primary restrictive cardiomyopathy was associated with complete heart block in four patients, two of whom had skeletal myopathy. One had a family history of dominantly inherited skeletal myopathy. Primary restrictive cardiomyopathy was present in a mother and daughter. Two other patients had a family history of heart failure, sudden death or complete heart block, alone or in combination, at a young age. Restrictive hemodynamics and complete heart block were present in patients even in the absence of significant fibrosis. The data suggest that primary restrictive cardiomyopathy may be a distinct myopathy with dominant inheritance and incomplete penetrance that is expressed morphologically as myocyte hypertrophy and interstitial fibrosis. Skeletal myopathy may be associated with the cardiomyopathy.

Laser angioplasty of restenosed coronary stents: results of a multicenter surveillance trial. The Laser Angioplasty of Restenosed Stents (LARS) Investigators.

OBJECTIVES: This study evaluated safety and efficacy of excimer laser angioplasty for treatment of restenosed or occluded coronary stents. BACKGROUND: Balloon angioplasty of in-stent restenosis is limited by a high recurrence rate. Debulking by laser angioplasty is a novel concept to treat in-stent restenosis. METHODS: A total of 440 patients with restenoses or occlusions in 527 stents were enrolled for treatment with concentric or eccentric laser catheters and adjunctive balloon angioplasty. RESULTS: Laser angioplasty success (< or =50% diameter stenosis after laser treatment or successful passage with a 2.0-mm or 1.7-mm eccentric laser catheter) was achieved in 92% of patients. Adjunctive balloon angioplasty was performed in 99%. Procedural success (laser angioplasty success followed by < or =30% stenosis with or without balloon angioplasty) was 91%. There was neither a significant difference in success with respect to lesion length, nor were there differences between small and large vessels or native vessels and vein grafts. Success was higher and residual stenosis lower using large or eccentric catheters. Serious adverse events included death (1.6%, not directly laser catheter related), Q-wave myocardial infarction (0.5%), non-Q-wave infarction (2.7%), cardiac tamponade (0.5%) and stent damage (0.5%). Perforations after laser treatment occurred in 0.9% of patients and after balloon angioplasty in 0.2%. Dissections were visible in 4.8% of patients after laser treatment and in 9.3% after balloon angioplasty. Reinterventions during hospitalization were necessary in 0.9% of patients; bypass surgery was performed in 0.2%. CONCLUSIONS: Excimer laser angioplasty with adjunctive balloon angioplasty is a safe and efficient technology to treat in-stent restenoses. These data justify a randomized comparison with balloon angioplasty.

Mechanical restitution of isolated human ventricular myocardium subjected to in vivo pressure and volume overload.

OBJECTIVE: The aim was to make a comparison of the mechanical and electrical refractory properties of isolated strips of human ventricular myocardium obtained from patients with either left ventricular pressure overload, volume overload, or normal left ventricular function. METHODS: Strips of ventricular myocardium were obtained at the time of cardiac surgery from 17 patients with aortic stenosis, representing pressure overload, 14 patients with aortic regurgitation, representing volume overload, and nine patients with mitral stenosis, representing normal left ventricular function. Muscle strips were mounted isometrically in a tissue bath, superfused with physiological saline at 37 degrees C, and stimulated at 1 Hz. Mechanical restitution curves were constructed from the isometric twitch tension obtained from extrastimuli during a special stimulus protocol. Transmembrane action potentials were recorded using glass microelectrodes and restitution of the upstroke velocity of action potentials studied in the presence of high external potassium concentration. RESULTS: The aortic stenosis group was older and had higher left ventricular systolic pressures and thicker left ventricular walls than the other groups. Electrocardiographic evidence of left ventricular hypertrophy was present in both the aortic stenosis and aortic regurgitation groups. Peak tension, time to peak tension, and the maximum rates of rise and fall of tension were not significantly different between groups. The time constant of the initial rapid recovery phase of mechanical restitution (tau 1) was prolonged in the aortic stenosis group, at 603(SEM 80) ms v 367(53) ms in the aortic regurgitation group (p < 0.005), and 259(70) ms in the mitral stenosis group (p < 0.005). There was a positive correlation between tau 1 and left ventricular wall thickness (p < 0.05). Neither "normal" nor "slow" (in the presence of raised external potassium) transmembrane action potentials differed in the groups studied. The mean time constant of recovery of "slow" action potential dV/dtmax was slower in the aortic stenosis group, but this difference was not significant. CONCLUSIONS: These data are consistent with the hypothesis that the rate of recovery of calcium release from the sarcoplasmic reticulum is slowed in myocardial hypertrophy due to pressure overload in man and provides a possible explanation of the occurrence of mechanical alternans in such patients.

A computerised dichromatic earpiece densitometer for the measurement of cardiac output.

This study assesses a precalibrated dichromatic earpiece densitometer and microprocessor for the measurement of cardiac output by indocyanine green dye dilution. The measured cardiac output is compared with values of cardiac output simultaneously determined using a cuvette densitometer. The microprocessor computation of cardiac output agreed very closely with the cardiac output determined by manual calculation from the same dye dilution curves (standard deviation +/- 1.47%). The reproducibility of the earpiece densitometer (standard deviation +/- 5.2%) was virtually identical to that of the cuvette densitometer (+/- 5.3%). In a comparison of earpiece and cuvette densitometers for 60 measurements of cardiac output following pulmonary arterial injection of dye and for 50 measurements following femoral venous injection of dye, correlation coefficients were 0.83 and 0.78 and the standard deviations of the differences of simultaneous measurements were 7.2% and 8.3% respectively. The instrument offers an accurate reproducible and relatively noninvasive technique for measuring cardiac output.

Inotropic and vasodilator effects of amrinone on isolated human tissue.

The effects of amrinone on human umbilical artery and human myocardium were studied. Amrinone produced dose related increases in tension, dT/dtmax and dT/dtmin in myocardium from patients who were NYHA grade I (n = 1) and II (n = 4). The responses to amrinone of these tissues were similar to the response seen in normal guinea-pig myocardium (n = 34). The drug had no inotropic effect on tissue from NYHA grade III patients (n = 5). The inotropic response of the tissues to amrinone was inversely related to length of history and severity of heart failure in the patients from whom the tissues were obtained. Amrinone caused dose related relaxation of the human umbilical artery. The vasodilator properties, but not the positive inotropic effects of amrinone were detectable at concentrations of the drug obtained during oral therapy (0.4 to 4.0 micrograms X ml-1). These findings support the view that in patients with congestive cardiac failure amrinone acts by vasodilatation with no clinically important positive inotropic effect.

Systolic and diastolic ventricular function in cardiac amyloidosis. Studies in six cases diagnosed with endomyocardial biopsy.

Five cases of cardiac amyloidosis diagnosed after endomyocardial biopsy are described. Systolic function was normal in three cases as assessed by cardiac index, ejection fraction and maximal velocity of contractile element shortening at zero developed pressure. The diastolic dip and plateau wave form was a characteristic but not an invariable finding. Increased ventricular end-diastolic pressure but normal end-diastolic volume indexes in all cases implied a disorder of diastolic compliance. The diastolic pressure-volume plots suggested a sudden decrease in distensibility after normal early filling of the ventricle. The functional defect did not necessarily differ from that of other diseases of heart muscle. Therefore, hemodynamic data should not be relied upon for diagnostic purposes. Electron microscopy was the most reliable aid in making the diagnosis from the endomyocardial biopsy specimens especially in the presence of fibrosis. It may not be valid to assume a diagnosis of cardiac amyloidosis from the finding of amyloid in other organs.

Late results of valvoplasty for mitral regurgitation due to rupture of chordae of the posterior (mural) cusp.

Nine patients with rupture of chordae tendinea of the posterior cusp of the mitral valve are presented. All have been treated by plication of the posterior cusp and atrial wall. The presenting postoperative features have been described: 89 per cent are markedly improved; two patients have normal heart sounds with no murmurs; 6 patients have only a Grade 1 pansystolic apical murmur. The advantages of this procedure compared with mitral valve replacement for the same condition have been presented.

Release of platelet activation markers during coronary angioplasty.

BACKGROUND: Authors of several studies have reported that activation of platelets occurs during coronary angioplasty, but consistent results have not been obtained. Levels of serotonin in coronary circulation have been found to be elevated during percutaneous transluminal coronary angioplasty but greater than normal concentrations of beta-thromboglobulin and platelet factor 4 have not been detected. OBJECTIVE: To perform a serial analysis of platelet-activation markers with simultaneous measurements of levels of serotonin, beta-thromboglobulin and platelet factor 4 in blood samples from the coronary artery and coronary sinus of patients undergoing coronary angioplasty. METHODS: Twenty patients undergoing elective coronary angioplasty were studied. Measurements of levels of beta-thromboglobulin, platelet factor 4, and serotonin in samples from the ostium of the coronary artery and the coronary sinus were performed immediately before angioplasty and after the first balloon deflation. RESULTS: Concentrations of beta-thromboglobulin and platelet factor 4 in coronary artery and coronary sinus were elevated in all patients before dilatation, whereas concentrations of serotonin were elevated in 85% of the patients. Concentrations of all markers in coronary sinus decreased after the first inflation. The coronary-sinus: coronary-artery concentration ratios before dilatation for beta-thromboglobulin, platelet factor 4, and serotonin were > 1 for the majority of patients, particularly for those with complex culprit lesions, indicating that coronary activation of platelets was occurring. Ratios remained unchanged or decreased after the first inflation, depending on initial values. CONCLUSIONS: Both systemic and coronary activation occur in patients subjected to percutaneous transluminal coronary angioplasty before the onset of intervention. After balloon deflation the greater than normal baseline coronary-sinus:coronary-artery concentration ratios of all markers (beta-thromboglobulin, platelet factor 4 and serotonin) tend to decline or remain unchanged, depending on the level of activation.

Predictors of the rate of success of angioplasty of the left circumflex artery.

Out of 45 angioplasties attempted by the same cardiologist for stenosis of the left circumflex artery at St. Thomas' Hospital in a one and a half year period, six were unsuccessful due to inability to cross the lesion. In four of these cases, the lesion was crossed with the guide wire but not with the balloon. All these failures, and sixteen of the successful cases, were studied by means of geometrical analysis of the anatomy of the circumflex artery and computer-assisted automated quantitation of digital subtraction coronary angiograms obtained at the time of the procedure. The quantitative characteristics of the lesion (the proportional diameter of the stenosis; the proportional geometric area of the stenosis and the proportional densitometric area of the stenosis) were not significantly different between the cases resulting in failure or success. Similarly, the angles of the circumflex artery proximal to the stenosis, the distance of the lesion from the orifice of the artery and the length of the main stem of the left coronary were not different between the two groups. The group in which the angioplasty was unsuccessful had significantly longer lesions, however, whereas the ratios of the diameter (or the geometric area) of the distal part of the vessel beyond the lesion as compared with the proximal (reference) part were significantly lower in the group undergoing successful dilatation. We conclude that neither the angulation of the circumflex artery as it appears on a two-dimensional projection nor the proportional diametric stenosis of the lesion can serve as easily assessible predictors fro the success of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angiography using a portable super-C-arm imaging system in a district general hospital.

BACKGROUND: New generation portable super-C-arm imaging systems may offer an alternative means of performing coronary angiography at a lower cost compared with a fixed laboratory. We evaluated the use of one such system (GE-OEC 9800) in a district hospital setting. METHODS: The demographics, procedure and screening times, emitted radiation dose and diagnoses of the first 200 consecutive patients were obtained from a prospective database. Comparison between the portable and fixed systems were made by analysing results from similar cohorts of patients who underwent angiography by the same operators. Image quality was assessed in 23 patients, by an independent cardiologist, comparing the GE-OEC 9800 angiograms with repeat images using a fixed laboratory Philips (HM 3000) system within 3 months of the first study. RESULTS: The procedure time (mean (S.D.)) was 18.9 (0.8) min for the 200 cases. The screening time was 255 (15) s with an emitted radiation of 22.8 (1.4) Gy/cm(2). Comparison between the C-arm and fixed systems revealed significantly longer screening time (230.6 (14.6) vs. 157 (12.9) s, p<0.001), whilst the total radiation doses were not significantly different (21.1 (1.5) vs. 18.6 (1.11) Gy/cm(2)). Independently assessed image quality was satisfactory. The main variance in 57 lesions seen in the 23 patients using the angiograms obtained from the fixed laboratory as reference included overestimated stenosis (two lesions), underestimated stenosis (or subsequent disease progression) (four lesions), lack of appreciation of side-branch ostial involvement (two lesions) and vessel calcification (one lesion). CONCLUSIONS: Portable imaging systems can offer a reliable and cost-effective diagnostic coronary angiography service in a district hospital.

201Tl scintigraphy in the assessment of patients with multi-vessel coronary disease undergoing angioplasty who have previously had a coronary bypass graft operation.

Percutaneous transluminal coronary angioplasty (PTCA) has an important therapeutic role in the treatment of coronary artery disease. The purpose of this study was to investigate the role of 201Tl scintigraphy in symptomatic patients with multi-vessel coronary artery disease undergoing angioplasty who had previously undergone coronary graft operations. 201Tl imaging was carried out in 12 patients prior to PTCA, 6 weeks and 6 months to 1 year post-PTCA. Prior to PTCA, 201Tl imaging correctly identified the site of the dominant lesion in all patients in correlation with the catheter results. Six weeks post-PTCA, seven cases who had angiographically successful angioplasty showed persistent defects on 201Tl imaging. In five of these cases, follow-up catheter showed that re-stenosis had occurred. Six months to 1 year post-PTCA, 201Tl imaging was found to have good correlation (11 out of 12 patients) with the catheter results. The results suggest that 201Tl imaging is useful in the management of patients with multi-vessel disease undergoing angioplasty.

Cannulation of the coronary sinus via the femoral vein--a new technique.

BACKGROUND: Cannulation of the coronary sinus usually has been accomplished by advancing a catheter through the sub-clavian or internal jugular veins. HYPOTHESIS: We have developed a new technique for cannulation of the coronary sinus with a modified 6F Judkins L5 coronary catheter positioned through the femoral vein. RESULTS: The technique was tried successfully in 20 consecutive patients by the same operator and the average fluoroscopy time for coronary sinus cannulation was 1.6 +/- 1.0 min. CONCLUSION: Analysis of the results showed evidence of a learning curve with improvement of time with an increasing number of patients. The method provides a safe and inexpensive solution for catheterization of the coronary sinus, easily accessible to every catheter laboratory.

Limitations of coronary angiography: an underestimated problem?

Angiographic imaging suffers from many limitations which may distort the diagnostic information obtained from coronary arteriograms. Radiographic features limiting precise coronary stenosis measurement are caused by the x-ray source, the image intensifier, and the chemical properties of the cinefilm. Biologic variations are introduced by fluctuations in angiographic contrast concentration and flow- or contrast-dependent coronary dilation. Random errors are also introduced by the selection of the radiographic projection and frame to be analyzed and the digitization of cineangiograms. These limitations and their significance in distorting quantitative information obtained from coronary angiograms are discussed in this review.

Is angiographic ventriculography necessary for the assessment of ischemic patients?

A total of 53 patients with a provisional diagnosis of ischemic heart disease and without any clinical evidence of valvular, congenital, or primary muscle heart disease were studied by echocardiography and biplane left ventricular cineangiography. For angiographic ejection fraction analysis, a program developed in our department for use on an Apple Macintosh computer interfaced to a digitizing tablet was employed. Echocardiographic outlines of systolic and diastolic images were traced with a digitizing system on the screen and ejection fractions were calculated by a program incorporated in the echo machine. Good echo windows allowing ejection fraction calculations were present in 35 patients. There was a good correlation between angiographic and echocardiographic ejection fraction (r = 0.7, SEE = 0.09), and wall motion assessment revealed no significant discrepancies between the two image modalities. The remaining 18 patients had poor echo windows, preventing accurate echocardiographic determination of the ejection fraction. However, limited assessment of left ventricular size and wall motion was possible in all patients and allowed the identification of those who had impaired left ventricular function as judged by angiography (angiographic ejection fraction < 35%). We conclude that even in patients with poor echo windows echocardiographic assessment of left ventricular function provides clinical information similar to angiography which should not be considered mandatory for the investigation of ordinary ischemic patients.

Echocardiographic left ventricular wall thickness: a poor predictor of the severity of aortic valve stenosis.

Echocardiographic left ventricular hypertrophy is thought to be helpful in grading the severity of aortic stenosis. This study compared M-mode echocardiographic left ventricular wall dimensions with Gorlin aortic valve area. Good quality echocardiograms were obtained in 294 patients with aortic stenosis who also underwent cardiac catheterization. Patients with grade 3 or 4 aortic regurgitation were excluded. The correlation was calculated between the aortic valve area and the left ventricular wall dimensions. Correlation coefficients were poor; r = 0.13 for the septum, r = 0.15 for the posterior wall, and r = 0.17 for the mean wall dimension. Correlation was not improved significantly if patients with poor left ventricular function or systemic hypertension were excluded. Correlation with other hemodynamic parameters was better, peak left ventricular systolic pressure having r values of 0.36 and 0.30 for posterior wall and septum. Mean and peak aortic valve gradient had r values approaching 0.30 for both dimensions. If the peak gradient was included in multivariate analysis, the wall dimensions then had no predictive power for severity of aortic stenosis. This study demonstrates that the degree of left ventricular wall hypertrophy is not related to the severity of aortic outflow obstruction and therefore cannot be used to grade the severity of aortic stenosis.

Functional aortic coarctation caused by thrombosis within a thoracic aortic aneurysm.

A 67 year old male arteriopath presented with chest pain, a new systolic murmur at the lower left sternal border and loss of leg pulses. Mitral regurgitation and ventricular septal defect were excluded by echocardiographic colour flow Doppler mapping and right heart catheterisation. CT scanning demonstrated a leaking aneurysm of the descending thoracic aorta with stenosis of the proximal lumen due to atheroma and thrombus causing a functional coarctation. The findings were confirmed at surgery.

Pulmonary vein blood flow velocity in pulsus paradoxus.

The effect of inspiration on pulmonary vein blood flow velocity and forward pressure gradient from pulmonary vein to left atrium was studied in seven patients with chronic constrictive pericarditis, five of whom had clinically obvious pulsus paradoxus. Compared to patients without pericardial disease, where inspiration produced no change, patients with pericardial disease showed an inspiratory fall in the forward pressure gradient and forward blood flow velocity in the pulmonary veins on inspiration. The mechanism of pulsus paradoxus in these patients can be explained by incomplete transmission of the inspiratory fall of intrathoracic pressure to the left atrium.