Door-to-balloon time in radial versus femoral approach for primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction

Primary percutaneous coronary intervention (pPCI) is considered the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction (STEMI). This study compares the door-to-balloon (D2B) time between transradial vs. the transfemoral approach in patients presenting with STEMI.MethodsA retrospectively collected catheterization laboratory database was reviewed for the consecutive patients presenting with a STEMI. Specific time parameters were recorded, and our composite end points were time to revascularization, angiographic success, short term clinical success, and procedural vascular complications.ResultsRadial PCI (r-PCI) was performed in 33 patients (67.3%) and in 16 patients (32.7%) PCI was done through femoral artery (f-PCI). No significant difference was observed in the pre-catheter and catheter laboratory times. Mean times from emergency room door-to-catheter laboratory time for r-PCI vs. f-PCI were 82.48 ± 37.42 and 76.29 ± 34.32 min, respectively (P = 0.636). The mean time from patient arrival to the cardiac catheter laboratory-to-balloon inflation was 34.56 ± 14.2 in the r-PCI group vs. 33.12 ± 12.56 min with the f-PCI group (P = 0.215). The total D2B time was not significantly different between r-PCI vs. f-PCI groups (100.32 ± 36.3 vs. 97.31 ± 30.37 min, respectively, P = 0.522). Angiographic success rates were observed in 92.1% of the patients for r-PCI, and in 87.5% for f-PCI (P = 0.712). There were no vascular complications in both groups.ConclusionsPatients presenting with STEMI can undergo successful pPCI via radial artery without compromising patient care.     

Pulmonary Hemodynamic Response to Acute Combination and Monotherapy With Sildenafil and Brain Natriuretic Peptide in Rats With Monocrotaline-Induced Pulmonary Hypertension

BackgroundThe lungs of patients with pulmonary arterial hypertension (PAH) exhibit decreased bioavailability of nitric oxide and downstream signaling through cyclic guanosine monophosphate (cGMP). Therapies that enhance cGMP-mediated vasodilation have shown efficacy in treating PAH. We tested the hypothesis that combination therapy with sildenafil, a cGMP phosphodiesterase type 5 inhibitor, and brain natriuretic peptide (BNP), a receptor-mediated guanosine cyclase stimulator, synergistically attenuates monocrotaline-induced PAH in rats compared with either monotherapy.MethodsAdult male Sprague-aDawley rats were subcutaneously injected with monocrotaline (n = 41, 50 mg/kg). After approximately 4 weeks, the rats were infused intravenously with vehicle solution, sildenafil (42 and 85 μg/kg/min), or BNP (50 and 100 ng/kg/min), alone and in varied combination. The primary endpoint was the relative change in right ventricular systolic pressure (RVSP) and mean arterial systemic pressure (MAP). Secondary endpoints included heart rate and dP/dt.ResultsVehicle infusions did not alter hemodynamic variables. Sildenafil₈₅ (85 μg/kg/min) alone decreased RVSP (? 16.6 ± 5.6%) and decreased MAP (? 4.0 ± 4.7%). BNP₅₀ (50 ng/kg/min) and BNP₁₀₀ (100 ng/kg/min) decreased RVSP (? 23.3 ± 5.7% and ? 27.1 ± 2.9%, respectively) and MAP (? 6.4 ± 5.8% and ? 14.3 ± 4.1%, respectively). Combination therapy with sildenafil₄₂ and BNP₅₀ decreased RVSP (? 20.7 ± 5.6%) and showed a lessened systemic effect (MAP = ? 11.6 ± 5.9%). Combination therapy with sildenafil₈₅ and BNP₁₀₀ decreased RVSP (? 27.6 ± 3.2%, P = NS) and showed increased systemic effect (MAP = ? 20.7 ± 3.1%, P < 0.05) in comparison with sildenafil₈₅.ConclusionsThis study suggests that intravenous administration of both sildenafil and BNP monotherapy produces significant improvement in RVSP, making them potentially viable options for the treatment of PAH, whereas combination therapy produces no additional improvement in pulmonary hemodynamics.     

Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats

ObjectiveWe compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance.MethodsFemale Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods.ResultsThere was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3 ± 0.09, 0.82 ± 0.08; p < 0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17 ± 0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3 ± 0.15, 1.11 ± 0.12) was significantly higher than controls (0.56 ± 0.13; p < 0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65.ConclusionWe conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.     

Low-Dose Cyclosporine Treatment in Chinese Nephrotic Patients With Idiopathic Membranous Nephropathy: An Uncontrolled Study With Prospective Follow-up

IntroductionThe optimal dose of cyclosporine A (CsA) in treatment of nephrotic proteinuria in idiopathic membranous nephropathy (IMN) remains inconclusive. We evaluated the efficacy and safety of low-dose CsA combined with low-dose prednisone as induction therapy for Chinese nephrotic patients with IMN.MethodsWe conducted a prospective observational cohort study in 18 patients with IMN and nephrotic proteinuria. Twelve patients were refractory to other immunosuppressive therapies. The initial dose of CsA was 1 to 1.5 mg/kg/d combined with 0.15 to 0.50 mg/kg/d prednisone. The dose of CsA was adjusted monthly by 20% to 30% according to efficacy and the 12-hour trough blood concentration (C₀) of CsA around 100 ng/mL for 6 months; when proteinuria was <1 g/d, CsA was tapered gradually to a dose of 0.6 to 1 mg/kg/d.ResultsTwo patients discontinued CsA because of refractory hypertension. The remaining 16 patients had been followed up for 44 ± 15 weeks. Remission was observed in 11 patients (68.8%: complete remission, 6 and partial remission, 5). The effective dose of CsA for remission was 2.1 ± 0.4 (1.5–2.5) mg/kg/d, and the mean C₀ of CsA was 92.5 ± 23.5 (58–124) ng/mL. All the 16 patients experienced well-controlled adverse effects, including hypertension (n = 12), hyperuricemia (n = 12), increase of serum creatinine (n = 2), etc.ConclusionsLow-dose CsA combined with low-dose prednisone was effective and safe as induction therapy in majority of Chinese nephrotic patients with IMN, including those refractory to other immunosuppressive regimens.     

Prevalence of abnormal gastric emptying in asymptomatic women with newly detected diabetes and its reversibility after glycemic control—A prospective case control study

ObjectiveEffects of systemic hyperglycemia and normoglycemia on gastric emptying in people with type 2 diabetes are not clear. The aim of the study was to investigate the gastric emptying time in people with newly detected diabetes before and after control of diabetes compared with healthy controls.MethodsGastric emptying to solid meal was studied in 30 asymptomatic women with newly detected diabetes before and after achieving euglycemia and compared with 20 healthy age, sex and weight matched controls using egg white labelled with Technetium 99 m Sulfur Colloid.ResultsDelayed gastric emptying was seen in 90% of women with diabetes and none in healthy controls. Lag phase was 83.1 ± 11.8 min in cases compared to 37.2 ± 4.0 in controls (p = 0.05). Gastric emptying at 4 h was 46.73% ± 4.84% in cases and 97.65% ± 0.59% in controls (p = 0.05).T50 was 250 ± 8.8 min in cases against 94.70 ± 5.10 min in controls (p < 0.05). After control of diabetes, lag phase normalized to 37.2 ± 4.0 min against 35.2 ± 4.6 min in controls. Similarly all other parameters also normalized after control of diabetes.ConclusionsDelayed gastric emptying to solids was seen in 90% of women with type 2 diabetes at the time of hyperglycemia and normalized after control of diabetes.     

Effects of hemodilution with a hemoglobin-based oxygen carrier (HBOC-201) on ischemia/reperfusion injury in a model of partial warm liver ischemia of the rat

BackgroundIschemia/reperfusion injury is an unavoidable complication in liver surgery and transplantation. Hemodilution with colloids can reduce postischemic injury but limits oxygen transport. Hemoglobin-based oxygen carriers have been evaluated as blood substitute and provide a plasma-derived oxygen transport. It was the aim of our study to evaluate the combined benefits of hemodilution with a better oxygen supply to reperfused liver tissue by the use of HBOC-201 (Hemopure^®).Material and methodsA model of partial warm liver ischemia in the rat was used. One group served as untreated control, the other groups were hemodiluted either with Ringer’s lactate, Dextran-70, HBOC-201 or a mixture of Dextran and HBOC-201. After reperfusion, intravital microscopy studies were done and tissue pO₂ levels and transaminases measured. Statistical analysis was done by one- and two-way ANOVA, followed by pairwise comparison.ResultsHemodilution with Ringer’s lactate did not show any improvement compared to the control group. Dextran and HBOC group were superior to the Ringer and control animals in all parameters studied. Leucocyte adherence in postsinusoidal venules improved from 569.03 ± 171.87 and 364.52 ± 167.32 in control and Ringer group to 131.68 ± 58.34 and 68.44 ± 20.31/mm² endothelium in Dextran and HBOC group (p < 0.001). Concerning tissue pO₂ levels, HBOC (23.4 ± 5.0 mmHg) proved to be superior to Dextran (7.9 ± 4.4 mmHg; p = 0.007).ConclusionHBOC was equivalent to Dextran in reducing I/R injury in the liver, but improved oxygenation of postreperfusion liver tissue.     

High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death

RationaleDonation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement.ObjectiveWe investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD.Methods and ResultsHearts of male Wistar rats underwent 20 min baseline perfusion with glucose (11 mM) and either high fat (1.2 mM palmitate; HF) or no fat (NF), 27 min global ischemia (37 °C), and 60 min reperfusion with glucose only (n = 7–8 per group). Hemodynamic recovery was 50% lower in HF vs. NF hearts (34 ± 30% vs. 78 ± 8% (60 min reperfusion value of peak systolic pressure*heart rate as percentage of mean baseline); p < 0.01). During early reperfusion, glycolysis (0.3 ± 0.3 vs. 0.7 ± 0.3 μmol*min^− 1*g dry^− 1, p < 0.05), glucose oxidation (0.1 ± 0.03 vs. 0.4 ± 0.2 μmol*min^− 1*g dry^− 1, p < 0.01) and pyruvate dehydrogenase activity (1.8 ± 0.6 vs. 3.6 ± 0.5 U*g protein^− 1, p < 0.01) were significantly reduced in HF vs. NF groups, respectively, while lactate release was significantly greater (1.8 ± 0.9 vs. 0.6 ± 0.2 μmol*g wet^− 1*min^− 1; p < 0.05).ConclusionsAcute, pre-ischemic exposure to high fat significantly lowers post-ischemic cardiac recovery vs. no fat despite identical reperfusion conditions. These findings support the concept that oxidation of residual fatty acids is rapidly restored upon reperfusion and exacerbates ischemia–reperfusion (IR) injury. Strategies to optimize post-ischemic cardiac recovery should take pre-ischemic fat levels into consideration.     

Shortened erythrocyte sedimentation rate evaluation is applicable to hospitalised patients

BackgroundWestergren method, commonly used for erythrocyte sedimentation rate (ESR) determination, is simple and inexpensive. However, the 60 min required for the test are disadvantageous, especially for those departments/facilities where prompt evaluation is necessary. We investigated the possibility that earlier ESR recordings might correlate with standard 60-minute ESR and/or be predictive of the latter.MethodsDemographic and clinical data were collected from 220 randomly chosen adult patients hospitalised for various diseases in a medical department. ESR, determined by slightly modified Westergren method, was recorded at 15, 30 and 60 min. Correlation coefficients (r) between the standard and early ESR measurements were calculated for the entire group and for the separate subgroups divided according to patient age, sex and presence of anaemia or of inflammation.ResultsMean ± SD age of the patients was 61.3 ± 19.6, 55% were males; 45% had some inflammatory condition. Mean ± SD ESR values (mm) at 15, 30 and 60 min were 9.0 ± 12.1, 21.4 ± 21.8 and 35.9 ± 27.5, respectively. A statistically significant correlation was found between ESR measurements at 15 and 60 min (r = 0.833, p < 0.001). However, the strongest correlation was observed between 30 and 60 min measurements (r = 0.926, p < 0.001), irrespective of age, sex and presence of anaemia or of inflammation. Based on the ESR determination at 30 min (X), the predicted ESR value at 60 min (Y) could be calculated by a simple equation: Y = 10.7 + 1.2X.ConclusionSixty-minute ESR values can be predicted by the 30-minute estimation. Shortening the test by half an hour might bear practical importance.     

Desflurane-induced postconditioning of diabetic human right atrial myocardium in vitro

AimWe tested the hypothesis that brief exposure to desflurane at the time of reoxygenation might be able to protect against hypoxia–reoxygenation injury in human myocardium from diabetic (insulin-dependent, ID; and non-insulin-dependent, NID) patients and non-diabetic (ND) subjects.MethodsThe force of contraction (34°C, stimulation frequency 1 Hz) in the right atrial trabeculae was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (at 3, 6 and 9%) was administered during the first 5 min of reoxygenation. The force of contraction at the end of the 60-min reoxygenation period (FoC₆₀) was compared in the study groups (means ± SD).ResultsIn the ND group, desflurane at 3, 6 and 9% (FoC₆₀: respectively 78 ± 10%, 84 ± 4% and 85 ± 12% of baseline) enhanced the recovery of FoC₆₀ compared with the ND-controls (53 ± 7% of baseline; P < 0.05). In the ID group, desflurane at 3% (61 ± 4%) did not modify the recovery of FoC₆₀ compared with the ID-controls (54 ± 6%), whereas desflurane at 6 and 9% (75 ± 11% and 81 ± 8%, respectively) enhanced the recovery of FoC₆₀ vs the controls (P < 0.05). In the NID group, desflurane at 3% (57 ± 5%) also failed to modify the recovery of FoC₆₀ compared with the NID-controls (52 ± 10%), while desflurane at 6 and 9% (80 ± 10% and 79 ± 7%, respectively) enhanced the recovery of FoC₆₀ vs the controls (P < 0.05).ConclusionDesflurane in vitro was able to postcondition diabetic (both ID and NID) human myocardium at 6 and 9%, but not at 3%.     

Single patch technique versus double patch technique in repair of complete atrioventricular septal defect

MethodsThis retrospective study included 145 consecutive patients who underwent complete atrioventricular (CAVSD) repair between January 2002 and January 2012. Peri-operative data were analyzed. Ninety-two patients had a two-patch technique (group A); 53 patients had a single-patch technique (group B).ResultsMean age was 13.17 ± 4.94 months (group A) versus 5.15 ± 1.52 months (group B), (p < 0.001). Mean weight was 9.87 ± 5.53 versus 5.23 ± 2.12 kg (p < 0.001). Down syndrome was present in 82 (90.2%) in group A and 48 (90.5%) in group B (p = 0.315). Aortic cross-clamp times in group A was 135.3 ± 19.6 min and group B 107.7 ± 21.4 min (p < 0.0001). Cardiopulmonary bypass times were shorter in group B (132.2 ± 24.3 min) than group A (159.42 ± 31.4 min) with p value <0.001. Chylothorax, post operative bleeding, ICU stay and hospital length were not significant. Reoperation for left atrioventricular valve insufficiency occurred in 5 patients (5.4%) in group A, one of them needed valve replacement and 3 patients (5.7%) in group B. Permanent pacemaker was required for postoperative heart block in 3 patients (3.3%) in group A and 2 patients (3.8%) in group B (p = 0.623). Hospital mortality was seen in 6 patients (6.5%) in group A and 3 patients (5.7%) in group B (p = 0.606).ConclusionsSingle-patch technique can be performed with the same results like the two patch technique with a significantly shorter aortic cross clamp and bypass time.     

Patent hemostasis and comparison of two compression devices after transradial coronary catheterization and intervention

AimThe aim of this study was to compare two compression devices after transradial coronary catheterization and intervention.MethodsOut of 280 consecutive patients who underwent cardiac catheterization and intervention (n = 74) as a part of a same-day discharge program, 140 patients were applied the TR Band (TB) compression device and 140 the Seal-One (SO) compression device. The time needed to achieve patent hemostasis, duration of compression and local complications were assessed.ResultsIn the TB group, patent hemostasis was achieved in 17.5 ± 10.3 min (min), in the SO group in 21.4 ± 10.5 min (p = NS). The duration of radial artery compression was 90.7 ± 38.4 min in the TB group and 64.0 ± 26.5 min in the SO group (p < 0.001). The incidence of hematomas ≥5 cm did not differ between the two groups (6.4% vs. 6.4%, p = NS), the incidence of hematomas larger than 10 cm was 0.7% in the TB group and 1.4% in the SO group (p = NS). No radial artery occlusion or other local complications were found.ConclusionPostprocedural radial artery compression with TR Band and Seal-One devices is associated with early patent hemostasis and a short duration of compression. The use of the Seal-One device was related to a shorter mean compression time in this study. No radial artery occlusion at discharge, nor any other local complications occurred following the radial artery compression, except for several clinically insignificant hematomas.     

Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: A Montreal–Ottawa New Emerging Team (MONET) study

AimThe aim of this study was to determine the differences and changes in total and high-molecular-weight (HMW) adiponectin levels among metabolically healthy but obese (MHO) postmenopausal women in response to acute hyperinsulinaemia.MethodIn this cross-sectional study, 55 non-diabetic overweight and obese postmenopausal women underwent a hyperinsulinaemic–euglycaemic clamp test to evaluate insulin sensitivity. Subjects within the upper tertile of insulin sensitivity were described as ‘MHO’ (n = 18), whereas those within the lowest tertile were considered ‘at risk’ (n = 18). Plasma total and HMW adiponectin levels were measured by ELISA at 0 (baseline), 90, 160 and 180 min during the clamp.ResultsAt baseline and at all time points during the clamp, MHO individuals had significantly higher total and HMW adiponectin levels than at-risk subjects (AUC: total adiponectin = 2506 ± 1010 vs 1616 ± 830; HMW adiponectin = 909 ± 307 vs 604 ± 349; P < 0.05). In addition, a significant reduction in total adiponectin was observed at 160 min and 180 min in at-risk and MHO subjects, respectively, while HMW adiponectin significantly decreased at 160 min in at-risk subjects, and at 90 min as well as 160 min in MHO women.ConclusionMHO postmenopausal women had higher levels of plasma total and HMW adiponectin than at-risk subjects at baseline and during the clamp. Furthermore, significant decreases in total and HMW adiponectin were observed at certain time points in both the MHO and at-risk subjects.     

Transient Induction of ANG II-Dependent Malignant Hypertension Causes Sustained Elevation of Blood Pressure and Augmentation of the Pressor Response to ANG II in CYP1A1-REN2 Transgenic Rats

IntroductionTransgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)] allow induction of various degrees of ANG II-dependent hypertension. Dietary administration of the aryl hydrocarbon indole-3-carbinol (I3C) at a dose of 0.15% induces a slowly developing form of ANG II-dependent hypertension, whereas dietary administration of a higher dose (0.3%) of I3C results in the development of ANG II-dependent malignant hypertension. Cessation of administration of 0.15% I3C results in the normalization of blood pressure, indicating the reversibility of hypertension induced by this dose of I3C. The present study was performed to determine if ANG II-dependent malignant hypertension is similarly reversible following cessation of dietary administration of 0.3% I3C.MethodsCyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% I3C for 11 days to induce malignant hypertension.ResultsCyp1a1-Ren2 rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (132 ± 3–229 ± 11 mm Hg, P < 0.001) and marked decreases in body weight (303 ± 4–222 ± 2 g, P < 0.001). When I3C administration was terminated, SBP decreased to 167 ± 4 mm Hg (P < 0.01) and body weight increased to normal levels (309 ± 2 g, P < 0.01) within 12 days. However, SBP remained significantly elevated (172 ± 1 mm Hg, P < 0.01) for up to 3 weeks after termination of dietary administration of 0.3% I3C. In addition, the magnitude of the blood pressure response to intravenous bolus administration of 50 ng of ANG II (50 μL in volume) 3 weeks after cessation of dietary I3C administration was substantially higher than that observed in normotensive control rats (134 ± 1 mm Hg, n = 6) not previously induced with 0.3% I3C (53 ± 2 versus 38 ± 3 mm Hg, P < 0.05).ConclusionsThe present findings demonstrate that transient induction of ANG II-dependent malignant hypertension results in prolonged elevations of arterial blood pressure and marked augmentation of the magnitude of the pressor response to ANG II in Cyp1a1-Ren2 transgenic rats.     

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus

AimsThis study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery.MethodsEighteen type 2 diabetics (age 55 ± 2 years) and twenty healthy controls (age 51 ± 1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade.ResultsThe parasympathetic effect on the RR interval was blunted (P = .004) in diabetic subjects during recovery. Parasympathetic effect on QT–RR slope during early recovery was diminished in the diabetes group (diabetes 0.13 ± 0.02, control 0.21 ± 0.02, P = .03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5 ± 1.9 bpm, control 27.6 ± 1.5 bpm, P < .001).ConclusionsIn subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.     

Progresión de la enfermedad renal crónica en pacientes con hipertensión resistente sometidos a 2 estrategias terapéuticas: intensificación con diuréticos de asa vs. antagonistas de la aldosterona

IntroductionActualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD).ObjectiveTo evaluate CKD progression in patients with resistant hypertension undergoing 2 diferent therapies: treatment with spironolactone or furosemide.MethodsWe included 30 patients (21 M, 9 W) with a mean age of 66.3 ± 9.1 years, eGFR 55.8 ± 16.5 ml/min/1.73 m², SBP 162.8 ± 8.2 and DBP 90.2 ± 6.2 mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41).ResultsThe mean annual eGFR decrease was -2.8 ± 5.4 ml/min/1.73 m². In spironolactone group was –2.1 ± 4.8 ml/min/1.73 m² and in furosemide group was -3.2 ± 5.6 ml/min/1.73 m², P<0.01. In patients received spironolactone, SBP decreased 23 ± 9 mmHg and in furosemide group decreased 16 ± 3 mmHg, P<.01. DBP decreased 10 ± 8 mmHg and 6 ± 2 mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model.ConclusionTreatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.     

Acute effect of sildenafil on myocardial ischemic territories in patients with stable coronary artery disease

ObjectivesTo test the safety of sildenafil in patients with stable coronary artery disease (CAD).MethodsSixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/placebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS.ResultsThe baseline mean segmental PSS in the sildenafil group changed by 52%, −3 ± 1% at baseline versus −7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, −7 ± 3% at baseline versus −7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (−15 ± 4% at baseline versus −18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (−14.8 ± 2% at baseline compared to −15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake.ConclusionSildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.     

Effect of type 2 diabetes on plasma kallikrein activity after physical exercise and its relationship to post-exercise hypotension

AimThe present study was undertaken to determine the effects of type 2 diabetes (T2D) on plasma kallikrein activity (PKA) and postexercise hypotension (PEH).MethodsTen T2D patients (age: 53.6 ± 1.3 years; body mass index: 30.6 ± 1.0 kg/m²; resting blood glucose: 157.8 ± 40.2 mg dL⁻¹) and 10 non-diabetic (ND) volunteers (age: 47.5 ± 1.0 years; body mass index: 28.3 ± 0.9 kg/m²; resting blood glucose: 91.2 ± 10.5 mg dL⁻¹) underwent two experimental sessions, consisting of 20 min of rest plus 20 min of exercise (EXE) at an intensity corresponding to 90% of their lactate threshold (90LT) and a non-exercise control (CON) session. Blood pressure (BP; Microlife BP 3AC1-1 monitor) and PKA were measured during rest and every 15 min for 135 min of the postexercise recovery period (RP).ResultsDuring the RP, the ND individuals presented with PEH at 30, 45 and 120 min (P < 0.05) while, in the T2D patients, PEH was not observed at any time. PKA increased at 15 min postexercise in the ND (P < 0.05), but not in the T2D patients.ConclusionT2D individuals have a lower PKA response to exercise, which probably suppresses its hypotensive effect, thus reinforcing the possible role of PKA on PEH.     

The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia–reperfusion injury

Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low [LMW] and high molecular weight [HMW]), which are localized to different cellular compartments, indicating unique biological activity. We previously showed that the LMW isoform is important in protecting the heart from myocardial dysfunction associated with ischemia–reperfusion (I/R) injury, but the roles of the HMW isoforms remain unknown. To elucidate the role of HMW isoforms in I/R and cardioprotection, hearts from novel mouse models, in which the murine FGF2 HMWs are knocked out (HMWKO) or the human FGF2 24 kDa HMW isoform is overexpressed (HMW Tg) and their wildtype (Wt) or non-transgenic (NTg) cohorts were subjected to an ex vivo work-performing heart model of I/R. There was a significant improvement in post-ischemic recovery of cardiac function in HMWKO hearts (76 ± 5%, p < 0.05) compared to Wt hearts (55 ± 5%), with a corresponding decrease in HMW Tg function (line 20: 38 ± 6% and line 28: 33 ± 4%, p < 0.05) compared to non-transgenic hearts (68 ± 9%). FGF2 LMW isoform was secreted from Wt and HMWKO hearts during I/R, and a FGF receptor (FGFR) inhibitor, PD173074 caused a decrease in cardiac function when administered in I/R in Wt and FGF2 HMWKO hearts (p < 0.05), indicating that FGFR is involved in FGF2 LMW isoform's biological effect in ischemia–reperfusion injury. Moreover, overexpression of HMW isoform reduced FGFR1 phosphorylation/activation with no further decrease in the phosphorylation state in the presence of the FGFR inhibitor. Overall, our data indicate that HMW isoforms have a detrimental role in the development of post-ischemic myocardial dysfunction.     

Electrocardiographic findings in hepatic cirrhosis and their association with the severity of disease

Purpose/aimPrevious studies reported prolongation of QT interval in cirrhotic patients. We aimed to investigate the electrocardiographic changes and their correlation with the disease severity in cirrhotic patients.MethodsSixty-nine cirrhotic patients were examined. The prolongation of corrected QT interval and low-voltage QRS in electrocardiography were cross-examined for clinical and biochemical data. The association of electrocardiographic findings with the severity of cirrhosis, as determined by both Child–Pugh and model for end-stage liver diseases (MELD) scores, was investigated.ResultsQT-interval prolongation was detected in 63.5% patients and 57.7% met the criteria for low-voltage QRS. Patients with prolonged QT-interval had higher Child scores (9.58 ± 2.5 vs. 8.16 ± 2.29 respectively, P = 0.04) but model for end-stage liver diseases scores was similar in those with prolonged QT and low-voltage electrocardiogram. The frequency of prolonged QT interval and low-voltage QRS were similar among patients with different Child–Pugh classes. Heart rate was also higher in patients with low-voltage electrocardiogram (89 ± 15 beats/min vs. 79 ± 16 beats/min, P = 0.01). Mean QRS voltage in precordial leads was lower in those with ascites (8.5 ± 2.6 mV vs. 11.8 ± 3.4 mV, P = 0.006).ConclusionElectrocardiographic changes are common in cirrhosis regardless of the disease severity. Low-voltage QRS may be related to anthropomorphic changes and development of ascites in these patients.     

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat

AimThe antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues.MethodsTo measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n = 6 and 13; tissue n = 4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n = 8 and n = 35, respectively) and for BK in various tissues less than 16% (n = 5-8).ResultsIn male Wistar rats (n = 3), plasma BK was 8.2 ± 6.6 fmol/mL (mean ± SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14 ± 3) and submaxillary gland (521 ± 315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89 ± 9) was not different from right renal BK (75 ± 23). Similarly, KA was comparable in the two kidneys (left 18.0 ± 1.5, right 15.8 ± 1.4 μkat/g).ConclusionAny possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.