Radial artery spasms impair invasive cardiological procedures' performance: a pharmacological approach to prevention and treatment.

The radial artery (RA) access is currently the gold standard to perform cardiovascular interventions. One of the more common limitations is radial artery spasm which is an often complication interrupting the procedure. Common risk factors associated with spasm include female gender, periprocedural anxiety, multiple puncture attempts, distal radial access, diabetes, hypertension, and smoking. The mechanism of spasm is complex and includes calmodulin and rho-kinase pathways leading to the smooth muscle contraction. Proper hydration, anxiety management, and adequate local anesthesia should be applied to decrease the risk of spasms. Radial cocktail is often used to prevent spasm. Its composition differs between catheterization laboratories and the effect is attributed either to the verapamil or nitroglycerin, with contradictory results of different studies. Balbay maneuver is also an effective mean of prevention. Hydrophilic-coated devices can be used both to avoid spasms or reverse them. Radial angiography can be used to differentiate spasm from a tortuosity and choose proper method of management. Fasudil, a Rho-kinase inhibitor, has been reported as a pharmacological method to prevent spasm and reverse radial artery spasm.

Relationship between hyperinsulinemia and angiographically defined coronary atherosclerosis in non-diabetic men.

BACKGROUND: Our aim was to estimate the relationship between hyperinsulinemia and angiographically validated coronary atherosclerosis. METHODS: 102 consecutive non-diabetic male subjects (age 48.9 +/- 9.6 years) with a body mass index 25.9 +/- 2.8 kg/m(2) referred to coronary angiography in our centre were studied. A 75-g oral glucose tolerance test (OGTT) was performed and the areas under the curve (AUC) of serum insulin and glucose were calculated. RESULTS: Discriminant analysis with stepwise forward variable selection revealed that in younger patients (<50 years), the following parameters affected positively the number of significant coronary lumen reductions: age (F=8.5, p=0.005), lnAUCinsulin (F=5.8, p=0.02), low HDL cholesterol (F=4.4, p=0.04), the smoking habit (F=4.1, p=0.05). In those >=50 years of age, exclusively age (F=5.8, p=0.02) and hyperuricemia (F=3.8, p=0.06) entered the final model. CONCLUSION: Our results indicate that in non-diabetic male subjects the association of hyperinsulinemia with the severity of coronary atherosclerosis is only seen in younger patients.

Effects of acute euglycemic hyperinsulinemia on urinary nitrite/nitrate excretion and plasma endothelin-1 levels in men with essential hypertension and normotensive controls.

Insulin stimulates the production of endothelin-1 (ET-1) and nitric oxide (NO) by isolated endothelial cells. Additionally, insulin-dependent glucose transport and insulin-mediated NO production partially share common elements in signal transduction. There are discordant data on plasma ET-1 levels during acute euglycemic systemic hyperinsulinemia in normotensive men and men with essential hypertension (EH) (known to be insulin-resistant), as well as on the relations between insulin sensitivity and vascular function. Our aim was to assess the response of approximate measures of whole-body generation of NO and ET-1 to acute euglycemic hyperinsulinemia in EH patients and controls. We studied 17 newly diagnosed untreated men with uncomplicated EH and 10 normotensive controls. Plasma ET-1 and urinary excretion of nitrite plus nitrate, stable NO metabolites (Uno(x)), were measured before and during a 3-hour hyperinsulinemic-euglycemic clamp. Both in hypertensives and normotensives, plasma ET-1 levels were reduced after 2 hours of the clamp (EH: baseline, 3.1+/-1.9 pg/mL; 2 hours, 1.9+/-1.2 pg/mL, P = .04 v baseline; controls: baseline, 4.2+/-2.6 pg/mL; 2 hours, 2.8+/-1.4 pg/mL, P = .04 v baseline). No significant changes in Uno(x) during the clamp were observed. Changes in Uno(x) during the clamp (deltaUno(x)) and differences in plasma ET-1 measured before the end and before the beginning of the clamp (deltaET-1) were correlated in the controls (r = .75, P = .01) but not in EH (r = -.01, P = .97). No parameter of glucose metabolism correlated with basal Uno(x), basal plasma ET-1, deltaUno(x), and deltaET-1, whether absolute or percent values, in either group. Thus, acute euglycemic hyperinsulinemia produces a decrease in plasma ET-1 in both EH patients and controls. The lack of correlation between deltaUno(x) and deltaET-1 under these conditions in EH may suggest an impairment of systems governing interactions between the NO-dependent pathway and ET-1. In addition, insulin actions on glucose metabolism and on the endothelial mediators appear dissociated.

Impaired response of the forearm resistance but not conductance vessels to reactive hyperemia in hypertrophic cardiomyopathy.

It has been suggested that in hypertrophic cardiomyopathy (HC), vascular abnormalities are not restricted to the heart. Flow-mediated dilation of peripheral conductance arteries (reflecting their endothelial function) has not yet been studied in HC. Our aim was to assess both flow-dependent dilation of the brachial artery and flow responses (dependent on resistance vessels) during forearm reactive hyperemia (RH) in nontreated HC patients. The authors studied 13 HC patients and 14 age- and sex-matched healthy controls. None of them exhibited any factors known to be associated with endothelial dysfunction. Using 7 MHz ultrasound, brachial artery diameter and Doppler flow velocity were measured continuously at baseline and throughout 1 min of RH following 5 min of forearm ischemia induced by inflation of a blood pressure cuff. Arterial diameter and RH flow are expressed as percent changes with respect to the baseline. Flow-dependent dilation was similar in the HC patients and control subjects (7.2 +/- 9.5% vs 9.9 +/- 10.4%, p>0.05). Compared to the control group, RH flow in HC was decreased; however, differences did not reach statistical significance until 60 sec of RH (112 +/- 102% vs 261 +/- 217%, p<0.05; HC vs controls). In HC patients, endothelial function of peripheral conductance arteries is preserved. Hence, a defect in the forearm arterial bed in HC seems to be limited to mechanisms maintaining the dilation of resistance vessels during decreasing RH flow.

Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension.

Our aim was to investigate systemic nitric oxide (NO) production and its potential determinants such as insulin resistance, dyslipidemia, and circulating methylated analogs of L-arginine in uncomplicated essential hypertension (EH). Nineteen newly diagnosed, untreated male subjects with mild pure uncomplicated EH and 11 normotensive controls were studied at rest after an overnight fast. The groups had comparable age, body mass index, creatinine clearance, cholesterol, fasting glucose, and insulin. In hypertensives, the urinary excretion rate of nitrite plus nitrate (Unox), an index of endogenous NO production, was depressed (56+/-17 vs. 77+/-23 micromol/mmol creatinine; p < 0.05), whereas plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, were increased (2.4+/-1.1 vs. 1.1+/-0.7 microM; p < 0.005). Circulating concentrations of symmetric dimethylarginine were similar in both groups (1.4+/-1.3 vs. 1.5+/-1.1 microM; p = NS). The L-arginine-to-ADMA ratio was reduced in hypertension (3.3+/-0.5 vs. 4.5+/-0.8; p < 0.001 for In-transformed data). There was no correlation between Unox and either the magnitude of insulin resistance or dyslipidemia in EH. Thus in male subjects with EH, endogenous systemic NO formation appears depressed, which is unrelated to accompanying insulin resistance or dyslipidemia. Circulating ADMA levels are increased in uncomplicated EH, which may be of potential relevance.

Effect of a hemodialysis session on plasma levels of endothelin-1 in hypertensive and normotensive subjects with end-stage renal failure.

BACKGROUND: Elevated plasma endothelin-1 (ET-1) was found in end-stage renal failure (ESRF). However, there are discordant reports on the influence of hypertension on plasma ET-1 in ESRF and on the effect of hemodialysis on ET-1 concentrations. AIM: To compare the time course of plasma ET-1 during hemodialysis in hypertensive (HT) and normotensive (NT) ESRF patients. METHODS: Plasma ET-1 and mean blood pressure (MP) were measured in 12 HT patients and 11 matched NT patients on maintenance hemodialysis at baseline (B), after a 2.5-3.5 h hemodialysis with ultrafiltration (P1) and after a subsequent 1 h isovolumic dialysis (P2). RESULTS: In HT patients, plasma ET-1 increased at P1 with no further change after P2 (B vs. P1 and P2, p < 0.05). In NT patients, ET-1 levels were similar at B, P1 and P2. In HT, but not in NT subjects, volume loss correlated with change of ET-1 at P1. In HT patients, MP fell during P1 and tended to return towards baseline at P2. In NT patients, MP dropped after P1 and remained lower also at P2. CONCLUSION: Hypertensive ESRF subjects exhibit potentiated ET-1 release on hemodialysis, possibly stimulated by volume depletion with sympathetic activation, which may attenuate hypotensive hemodialysis effects thus contributing to hypertension in ESRF.

Evaluation of plasma cyclic GMP assay as a screening test for detection of acute cardiac allograft rejection.

Our aim was to assess the value of a single determination of plasma cyclic guanosine 3',5'-monophosphate (cGMP) in noninvasive screening for acute cardiac allograft rejection warranting augmentation of immunosuppression. Plasma cGMP levels were measured in 26 patients 1 to 13 months after heart transplantation on the same day the endomyocardial biopsies were performed. Acute moderate rejection (ISHLT 3A or 3B) was found in 10 out of 17 subjects (59%) with plasma cGMP >5 nmol/L, whereas there was mild or no rejection (ISHLT 0 to 1) in 8 from among 9 subjects (89%) with cGMP <5 nmol/L. Because cGMP levels <5 nmol/L appear to argue against the presence of acute rejection requiring therapy modification, our preliminary results suggest that a single plasma cGMP assay might be helpful in establishing indications for endomyocardial biopsy in heart transplant recipients.

The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure.

BACKGROUND: Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also affected. METHODS: The effect of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well as renal excretion of calcium and phosphate was studied under euglycaemic conditions (glucose clamp technique) in patients with advanced renal failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 micromol/l) and 12 control subjects were included. All subjects underwent a 3-h euglycaemic clamp with constant infusion of insulin (50 mU/m2/min) following a priming bolus. The urine was collected for 3 h before and throughout the clamp. RESULTS: The tissue insulin sensitivity (M/I) was lower in patients with renal failure than in control subjects (5.3+/-2.4 vs 6.7+/-1.8mg/kg/min per mU/ml, P= 0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calcium excretion increased (P < 0.05) and phosphate excretion did not change during the clamp in both groups. Despite a decrease of serum ionized calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but this effect was still significant after 180 min only in the renal failure group. A significant correlation was observed between changes in serum phosphate and PTH induced by hyperinsulinaemia (r = 0.48, P < 0.01 ) CONCLUSIONS: Phosphate-lowering effect of insulin is well preserved in severe renal failure despite the resistance to insulin-stimulated glucose uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.

Verapamil normalizes the response of left ventricular early diastolic filling to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

The aim of the study was to assess the left ventricular (LV) diastolic filling response to the cold pressor test in asymptomatic or mildly symptomatic patients with nonobstructive hypertrophic cardiomyopathy (HC) before and after verapamil therapy. The cold pressor test-induced alterations in LV filling pattern were additionally compared between HC patients and healthy control subjects. The cold pressor test, producing alpha- and beta-adrenergic stimulation, differentiates paradoxical coronary vasoconstriction due to endothelial dysfunction from the normal endothelium-dependent vasodilation. Such opposite coronary vasomotion at cold pressor test may be reflected by different responses of LV diastolic filling to the cold pressor test. Doppler echocardiography was performed in 10 asymptomatic or mildly symptomatic patients with nonobstructive HC as well as in 10 age- and sex-matched healthy subjects before and immediately after the cold pressor test. In HC patients before verapamil therapy, the cold pressor test induced a significant decrease in LV early filling parameters, contrary to healthy subjects, in whom the cold pressor test improved early filling [changes in early diastolic LV velocity -6.2 +/- 7.3 (-11.4 to -0.98) vs. 7.5 +/- 8.9 (1.13-13.86) cm/s, P = 0.0014, and changes in its acceleration rate -136 +/- 119 (-221 to -51) vs. 252 +/- 181 (122-381) cm/s2, P = 0.0001, respectively]. Verapamil therapy restored the normal pattern of the LV early filling response to the cold pressor test [changes in early diastolic LV velocity -6.2 +/- 7.3 (-11.4 to -0.98) vs. 5.3 +/- 3.4 (2.86 to 7.73) cm/s, P = 0.0003, and changes in its acceleration rate -136 +/- 119 (-221 to -51) vs. 328 +/- 185 (196 to 460) cm/s2, P = 0.0001, respectively]. Verapamil normalizes the LV early filling response to the cold pressor test in asymptomatic or mildly symptomatic patents with HC.

Determinants of depressed left ventricular ejection fraction in pure mitral stenosis with preserved sinus rhythm.

BACKGROUND AND AIM OF THE STUDY: Although depressed left ventricular ejection fraction is present in a considerable proportion of subjects with pure mitral stenosis (MS), its mechanisms are not clearly identified. The purpose of this study was to identify determinants of depressed ejection fraction in young patients with isolated mitral stenosis in sinus rhythm. METHODS: We retrospectively analyzed 320 records of patients with MS (mitral valve area < or = 2.0 cm2) who underwent invasive diagnostic procedure in our center. Of these 39 subjects aged 20-40 years with isolated MS in sinus rhythm were selected for the final analysis. RESULTS: An ejection fraction not exceeding 50% was found in 12 patients (group A). When comparing group A to the remainder (group B), group A patients had lower left ventricular end-diastolic volume indices (60.5 +/- 21.6 ml/m2 vs. 76.1 +/- 16.1 ml/m2, p = 0.02) and stroke volume indices (28.0 +/- 10.4 vs. 47.9 +/- 12.0, p < 0.001). No significant differences between the groups in patients' age, end-systolic volume index, mitral valve area, mean transmitral gradient, left-sided cardiac pressures, pulmonary wedge pressure, systemic vascular resistance, and cardiac output were found. Indices of left ventricular isovolumic contraction and relaxation as well as end-systolic indices of left ventricular function were also comparable. Group A had significantly higher pulmonary vascular resistance, pulmonary artery pressures, and higher heart rate. An approximate index of left ventricular compliance was significantly lower in group A with similar left ventricular minimal and end-diastolic pressures. CONCLUSIONS: Depressed ejection fraction in pure mitral stenosis with preserved sinus rhythm seems attributable to left ventricular underfilling that appears to be precipitated by other factors in addition to a narrowed mitral orifice, e.g. decreased passive left ventricular compliance and/or altered interventricular interactions.

Effect of having a functioning cadaveric renal transplant on cardiovascular mortality risk in patients on renal replacement therapy.

Our aim was to estimate the effect of having a functioning cadaveric renal transplant on the risk of cardiovascular and total mortality in patients on renal replacement therapy (RRT). We retrospectively studied (by the Cox proportional hazards regression model) 195 subjects who began RRT with maintenance dialysis in our centre from 1 January 1978 to 31 December 1991. Out of this number, 76 patients received a cadaveric kidney transplant. Cardiovascular abnormalities at the onset of RRT were the principal independent determinant of both total and cardiovascular mortality risk. As compared to patients on dialysis with the same duration of RRT, patients with a functioning renal transplant for more than 1 year had a significantly lower total mortality risk (mean relative risk (RR): 0.48 (0.25-0.91) (95% confidence limits in parentheses), P = 0.03), an effect whose significance disappeared after adjustment for pretreatment conditions (RR = 0.62 (0.30-1.30), P > 0.3). However, the beneficial effect of a functioning renal transplant for more than 1 year on cardiovascular mortality risk was significant, both before (RR = 0.21 (0.06-0.74), P = 0.02) and after the adjustment for pretreatment conditions (RR = 0.32 (0.11-0.90), P = 0.035). During the first year after a successful transplantation the beneficial effect of having a functioning transplant on cardiovascular mortality risk was only weakly attenuated. During RRT a functioning cadaveric renal transplant decreases cardiovascular mortality risk partially independently of the better pretreatment status of the patients selected for transplantation.

Plasma ANP and cyclic GMP levels versus left ventricular performance at different AV delays in AV sequential pacing.

Eleven resting patients with an implanted DDD pacemaker were studied. After 30 minutes of AV sequential pacing at a rate of 80 beats/min with three consecutive atrioventricular delays (AVDs; 100, 150, and 200 msec) peripheral venous blood was drawn for further analyses by specific radioimmunoassays of atrial natriuretic peptide (ANP) and the ANP second messenger, cyclic guanosine monophosphate (cGMP). Relative changes in left ventricular (LV) stroke volume following alterations of AVD were assessed by means of pulsed-Doppler echocardiography through measurement of LV outflow time-velocity integrals (TVI). The optimal AVD (oAVD) was defined in individual patients as that which was associated with the greatest TVI and with improvement over both other AVDs of more than 4%. The oAVD was found in nine patients. For these nine patients no significant differences in either plasma ANP or cGMP between various AVDs were observed. However, we found such differences with respect to values measured at oAVD; both ANP and cGMP levels were lowest at oAVD. Pooling together the data obtained in 11 patients at three AVDs, a positive correlation between ANP and cGMP levels was found (r = 0.7, P < 0.0001, n = 33). Moreover, changes of plasma ANP and cGMP induced by every AVD increment of 50 msec were also correlated (r = 0.6, P < 0.01, n = 22). It is concluded that in AV sequential pacing at rest plasma ANP reaches minimal levels at the AVD, which provides the best LV performance. Although levels of cGMP changed in parallel with those of ANP, low relative values of cGMP differences may limit the usefulness of cGMP assays in optimization of the AVD.

Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension.

The aim of this study was to assess the effects of L-arginine in primary pulmonary hypertension (PPH). Diagnostic cardiac catheterization was performed in 4 patients (pts) (1 man and 3 women, aged 18-47 years) with suspected PPH. In all of them diagnosis of PPH was confirmed; mean pulmonary artery pressure (PAP) ranged from 46 to 83 mmHg. Then 61/min oxygen was administered for 10 min through the oxygen mask (first oxygen test). After another 15 min, L-arginine was infused into an antecubital vein at a dose of 12.63g of L-arginine hydrochloride in 300 ml of 0.9% NaCl over 90 min. 15 min before the planned termination of the infusion the second oxygen test was performed in the same way as the first one. Hemodynamic data were collected by means of two catheters placed in the main pulmonary artery and in the aortic root. Cardiac output (CO) was estimated by the thermodilution technique. Blood samples were drawn from both catheters to estimate oxygen tension and cyclic GMP (cGMP) levels. In pts 1 and 2 differences between baseline values and following L-arginine did not exceed 9% for mean PAP (mPAP), total pulmonary resistance (TPR), mean aortic pressure (mAP), systemic resistance (SR), CO and HR. In patient 3 mAP and SR dropped by about 30%. In patient 4 after 15 min of the infusion mAP and SR fell by about 50%, whereupon we stopped L-arginine administration. Thus, for ethical reasons, we decided not to recruit new subjects for the study. In pts 1-3 aortic oxygen tension diminished by 10-15% on L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects.

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = -0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.

Influence of verapamil on the coronary arteriovenous difference in long chain free fatty acids in hypertrophic cardiomyopathy.

The percentage composition of free fatty acids in the coronary circulation has been studied during the passage of blood through the heart in patients with hypertrophic cardiomyopathy. Under basal conditions the percentages of palmitic and stearic acid decreased significantly. Verapamil i.v. produced a tendency towards a preferential myocardial uptake of oleic acid.

[Comparison of the value of echocardiographic examination in relation to hemodynamic studies in atrial septal defect of the ostium secundum type]. / Porównanie wartosci badania echokardiograficznego w odniesieniu do badan hemodynamicznych w ubytku miedzyprzedsionkowym (ASD) typu ostium secundum.

The aim of the study was in comparative analysis of the results obtained using the cardiac catheterization and the echocardiographic parameters in patients with atrial septal defect of the ostium secundum type. The studies have been performed in the group of 31 patients aged 16 to 58 years (mean = 31.9) in whom the right heart catheterization of the two-dimensional or Doppler's echocardiography has been performed. The following parameters have been analysed: pulmonary flow (Qp), systemic flow (Qs), shunt size (S), the Qp/Qs ratio, the systolic gradient via tricuspidal valve (TPG). The highest correlation in the invasive and the not invasive examination has been shown for TPG (r = 0.93). Other parameters showed no statistically significant differences.

Myocardial extraction of lactates, non-esterified fatty acids and their fractions in patients with dilated cardiomyopathy at rest and after the cold pressor test.

UNLABELLED: A decrease in the myocardial extraction or excretion of lactates indicates its hypoxia. The authors analyzed changes in the extraction of lactates, non-esterified fatty acids (NEFA) and their fractions: C 14:0, C 16:0, C 16:1, C 18:1, C 18:2 in a group of 15 patients with dilated cardiomyopathy (DC) and in 10 controls at rest and after the cold pressor test (CPT). At rest, 5 patients with DC produced lactates or extracted less than 10%. During CPT, production of lactates was observed in another four patients (mean values: 17.9 +/- 32.6% vs 24.5 +/- 5.2%, ns). NEFA extraction was found in the DC group: 18.4 +/- 20.6% vs. 13.9 +/- 33.3% /p < 0.05/). The acids involved were C 14:0, C 16:0, C 16:1 and C 18:0. In the controls, NEFA extraction did not change significantly: 12.1 +/- 8.6% vs 29.7 +/- 33.2%. CONCLUSIONS: 1. In part of patients with DC, production of lactates was found. The degree of lactate excretion increased due to CPT; 2. In DC, adrenergic stimulus (CPT) impairs the myocardial utilization of NEFA. This applied mainly to myristic acids, palmitic acid, palmitooleic acid and stearic acid; 3. This phenomenon probably is a result of profound functional and morphological damage to the mitochondrial system in DC.