Three different bradycardic agents, zatebradine, diltiazem and propranolol, distinctly modify heart rate variability and QT-interval variability.

Zatebradine, diltiazem and propranolol are all antiarrhythmic agents, and all induce bradycardia, but each is known to have a different initial molecular mechanism: zatebradine is a channel blocker of the hyperpolarization-activated inward current (I(f)); diltiazem is a blocker of the L-type Ca(2+) channel (I(CaL)), and propranolol is a beta-blocker. To further investigate the mechanisms underlying their clinical effects, we studied their effects on heart rate variability (HRV) and QT-interval variability (QTV). To this end, guinea pigs were treated with either zatebradine (1.5 mg/kg, i.p.), diltiazem (40 mg/kg, i.p.) or propranolol (20 mg/kg, i.p.). A dose of each agent that decreased HR by 20-22% was used in this study. HRV and QTV were analyzed by a fast Fourier and/or a wavelet transform algorithm. Zatebradine, an I(f) channel blocker, had no significant effect on HRV and QTV. Diltiazem, a non-dihydropyridine I(CaL) blocker, increased high frequency (HF) power and decreased the power ratio of the low frequency (LF) range to the HF range (L/H) in HRV, and increased QTV. Propranolol, a non-selective beta-antagonist, decreased LF power and L/H ratios in HRV, and appreciably reduced QTV. These differences in pharmacological action may help us better understand the antiarrhythmic and/or proarrhythmic actions of these agents when they are used clinically for reducing HR.

Simplified elephant trunk technique promotes thrombo-occlusion of the false lumen in acute type A aortic dissection.

OBJECTIVE: We developed a "simplified elephant trunk (SET) graft technique" as a refinement of the original elephant trunk. A cuff is created in a single 4-branched graft, which is used for the distal anastomosis; the residual distal graft is used as the trunk. We expected the SET would secure the anastomosis and promote the thrombo-occlusion of the false lumen in the down stream of the aorta. In this paper, we highlight the usage of the SET for arch replacement of acute aortic dissection cases in comparison with the same arch replacement without the SET method. PATIENTS AND METHODS: Between March 1996 and March 2002, 35 patients underwent arch replacement for acute aortic dissection. Twenty-two of them had a patent false lumen in the downstream aorta at the operation and 17 (SET: 8, non-SET (NSET) : 9) out of 22 underwent enhanced computed tomography (CT) scan 2 weeks after and 1 year after operation. We calculated the ratio of the false lumen in the aorta (F ratio) and the ratio of the patent false lumen in the whole false lumen (E ratio) by CT scan. These values were calculated every 3 cm down to 15 cm below the anastomosis, thus resulting in 5 segments. RESULTS: The false lumen throughout all segments disappeared (F ratio =0) in none of both group 2 weeks after operation. One year thereafter, in 5 (63%) patients in the SET group, no false lumen in any segment existed, while in contrast a false lumen still existed in some of the segments in all NSET patients. Although neither the F and E ratio of the NSET group change during this period in any segments, those of the SET group decreased significantly in all the segments except for the E ratio of segment 5. CONCLUSION: The SET promoted thrombo-occlusion thus leading to the disappearance of the residual false lumen, possibly by avoiding persistent endoleakage at the anastomotic site.

Reversal of delayed-onset paraplegia with thrombectomy of an interposed graft for the intercostal artery after thoracic descending aortic aneurysm repair.

A 78-year-old woman who had previously undergone prosthetic graft replacement of the total aortic arch was admitted to repair a chronic expanding type IIIb dissecting aneurysm. Firstly the patient's abdominal aorta was replaced with a prosthetic graft without any complications, then the thoracicdescending aorta was repaired five months later. Surgery for the thoracic descending aorta was performed with distal perfusion, cerebrospinal fluid drainage, somatosensory evoked potential (SEP) monitoring and reimplantation of three pairs of intercostal arteries. During surgery, SEP showed no significant changes, and the patient awoke without paraplegia three hours after the surgery. However, she developed bilateral complete paraplegia eight hours after the surgery. Reexploration demonstrated thrombo-occlusion of the sidearm graft for reimplantation of the Th10 intercostal artery. After thrombectomy of the sidearm graft, there was gradual neurological recovery and the patient was ambulatory when discharged. Quick treatment to restore the spinal cord blood supply promoted recovery from paraplegia.

Distinction between steady-state inactivation and voltage-dependent facilitation in L-type Ca2+ channel alpha1c and alpha1c/beta subunits.

The L-type Ca2+ channel has a unique kinetic property known as voltage-dependent facilitation. Many researchers have repeatedly investigated the mechanism in response to the voltage-dependent facilitation since the first observation by Fenwick et al. in 1982. Electrophysiological evaluations of voltage-dependent facilitation, however, remain inconsistent, partially because of its unclear definition. Some scientists understand it as a current augmentation by a conditioning prepulse prior to the test pulse, and others understand it as a result of the U-shape steady-state inactivation curve. We therefore investigated to identify the distinction between the voltage-dependent facilitation and the steady-state inactivation, by use of Ba2+ as the charge in order to avoid the other inactivation mechanism or the Ca(2+)-dependent inactivation upon this analysis. Conventional whole-cell mode patch clamp technique was applied to chinese hamster fibroblast (CHW) cells that express the alpha1c subunit alone or the alpha1c subunit with the beta subunit (alpha1c/beta) derived from rabbit heart to investigate the voltage-dependent facilitation depending on the composition of the subunits. Coexpression of the beta subunit augmented alpha1 subunit channel current and shifted current-voltage relation towards hyperpolarized direction. In the experiment using conventional double pulse protocol to investigate steady-state inactivation, alpha1c subunit channel current and alpha1c/beta subunit channel current were not fully inactivated. Subtraction of the steady-state inactivation component from whole recovered current enabled us to identify the voltage-dependent facilitation component of the L-type Ca2+ channel. The voltage-dependent facilitation of the alpha1 subunit current and the alpha1c/beta subunit current were identical in kinetics, and could be generated at 0 mV or depolarized potentials partially overlapped with the potential range for the steady-state inactivation of the current. These results suggest that the voltage-dependent facilitation of the L-type Ca2+ channel could be formed by the alpha1c subunit without interaction with the beta subunit, and that the range for the voltage-dependent facilitation and the steady-state inactivation overlap each other at 0 mV or more depolarized potentials up to approximately + 100 mV.

Aortic valve lipomatous hamartoma in a young woman.

We present a rare case of lipomatous hamartoma of the aortic valve. A 17-year-old woman was admitted with cardiac murmur. Echocardiography demonstrated severe aortic regurgitation and a highly echoic mass on the right cusp of the aortic valve. Surgery was performed with a differential diagnosis of chronic infective endocarditis or aortic valve tumor. At operation, a yellowish bead-shaped tumor was detected on the right cusp of the aortic valve, and aortic valve replacement was performed. Histopathological examination confirmed a lipomatous hamartoma. To the best of our knowledge, this is the first reported case of a lipomatous hamartoma located on the aortic valve.

Pinhole rupture of aortic root aneurysm with severe atherosclerotic change.

We report two cases of the rupture of calcified aortic root aneurysms that were successfully treated by emergency operations. One patient underwent Bentall's operation, and for the other, we performed a valve-sparing operation. Because their aneurysms revealed pear-like configurations with aortic regurgitation, the findings were consistent with annuloaortic ectasia (AAE). However, both cases were unlike typical AAE in that the aortic walls showed severe atherosclerotic change, with little sign of cystic medial necrosis. It was very interesting that each rupture point was a very small pinhole originating from one of the atherosclerotic ulcers.

Relationship Between Pump Speed Design and Hemolysis in an Axial Flow Blood Pump.

In an attempt to reduce the hemolysis caused by axial flow blood pumps, we investigated whether the specific speed should be kept within the standard engineering range or whether pump speed should be minimized, thus making the specific speed beyond the standard range. Four pumps with 11.8 mm diameter impellers were designed to accommodate a flow of 5 L/min and a head of 100 mm Hg. The pumps were tested at 4 speeds: A, 14,000; B, 18,000; C, 22,000; and D, 26,000 rpm. Pump performance data were obtained, and the maximum point of total pump efficiency was found for each pump. The maximum efficiencies were A, 50%; B, 58%; C, 52%; and D, 53%. The specific speed of each pump recorded at the maximum efficiency point was calculated as A, 899; B, 954; C, 1,218; and D, 1,951 rpm. Hemolytic tests were performed with fresh goat blood in a closed, mock-loop circuit. Hemolytic indexes were A, 0.036; B, 0.22; C, 0.35; and D, 0.66. We have concluded that decreased hemolysis is correlated with a lower pump speed and that the specific speed for the lowest pump speed is less than the standard range. Having a specific speed outside the standard range was not correlated with reduced total pump efficiency.

The gating and conductance properties of Cav3.2 low-voltage-activated T-type calcium channels.

Calcium channels are essential for excitation-contraction coupling and pacemaker potentials in cardiac muscle cells. Whereas L-type Ca(2+) channels have been extensively studied, T-type channels have been poorly characterized in cardiac myocytes. We describe here the functional properties of recombinant Ca(V)3.2 T-type Ca(2+) channels expressed in mammalian cell lines. The T-type Ca(2+) current showed a rapid activation and an inactivation phase in response to depolarization, and it displayed a window current over the voltage range from -60 to -40 mV in 1 to 10 mM external Ca(2+). Barium (Ba(2+)) and strontium (Sr(2+)) permeate the channel with similar activation kinetics. On the other hand, monovalent cations, Li(+) and Na(+), permeate the T-type Ca(2+) channel more easily than the L-type Ca(2+) channel. The permeability order of the Ca(V)3.2 T-type Ca(2+) channel among monovalent and divalent cations was determined as Ba(2+)>Mn(2+)>Ca(2+)>Sr(2+)>Li(+1)>Na(+) with the permeability order of 1.39:1.25:1.00:0.95:0.55:0.29. The ionic conductance sequence for cations relative to calcium was Sr(2+)>Ba(2+)>Ca(2+)>Li(+1)>Mn(2+)>Na(+) with the conductance ratio of 1.39:1.21:1.00:0.40:0.23:0.11. The permeation profile of manganese (Mn(2+)) is complex. Mn(2+) permeates the Ca(2+) channel with a permeability similar to Ca(2+) or Ba(2+), but with a much smaller current density, resulting in a much smaller conductance. The properties relating to progression and recovery from inactivation in the Ca(V)3.2 channel are substantially identical with either Ca(2+) or Ba(2+) as the charge carrier.

Improved hypertrophic obstructive cardiomyopathy by left ventricular apex epicardial pacing.

We report a case of severe hypertrophic obstructive cardiomyopahy (HOCM) that was markedly improved by left ventricular (LV) apex epicardial pacing. A 55-year-old woman with HOCM had suffered from dyspnea. Cardiac catheter examination showed a resting pressure gradient across the LV outflow tract of 198 mmHg despite combined medication. During the examination, right dual-chamber pacing could not sufficiently reduce the pressure gradient. Therefore, we treated the patient with LV apex epicardial pacing. The procedure decreased the pressure gradient to 10 mmHg. Clinical symptoms were markedly improved. LV apex epicardial pacing may be an alternative therapy for patients with HOCM who are refractory to other medical treatment.

MRSA aortic valve endocarditis treated by pericardium-lined Dacron patch and vancomycin-containing fibrin glue.

A 40-year-old man was admitted with a diagnosis of MRSA aortic valve endocarditis. He was treated conservatively with clindamycin and vancomycin for three days, but embolism occurred into the brain and the right lower limb, and urgent aortic valve replacement was performed. Resecting an aortic annular abscess resulted in a huge defect of the root. The defect was reconstructed with a combined patch: a Dacron graft lined with pericardium using vancomycin-containing fibrin glue. Although complete healing of the infected leg wound was slow, no prosthetic valve endocarditis has been detected in the 11 months since operation.

Patency of saphenous vein coronary artery bypass grafts from the vascular prosthesis of the ascending aorta.

BACKGROUND: Patients who have Stanford type A aortic dissection with impaired coronary arteries or who have aneurysms from the ascending aorta to the aortic arch with coronary artery disease need coronary artery bypass grafting (CABG) with tube graft replacement of the ascending aorta simultaneously. When vein grafts are used for CABG in these patients, the proximal anastomoses of vein grafts are attached to the prosthetic tube graft of the ascending aorta. However, the validity of proximal anastomoses of vein grafts to the prosthetic tube graft of the ascending aorta has not been confirmed. PATIENTS AND METHODS: We retrospectively analyzed patients who underwent venous coronary bypass grafting with prosthetic graft replacement of the ascending aorta. Between January 1984 and October 2002, 35 patients underwent CABG using saphenous vein grafts at the time of tube graft replacement of the ascending aorta, and the proximal anastomoses of the vein grafts were attached to the tube graft of the ascending aorta. Thirty-three venous bypass grafts were analyzed in 24 survivors. RESULTS: The postoperative catheterization showed only one early vein graft occlusion of 16 vein grafts anastomosed distally to the left anterior descending artery (LAD). All 14 venous grafts anastomosed to the right coronary artery (RCA) and 3 to the left circumflex artery (LCX) were patent. Therefore, the postoperative patency rate at discharge was 97.0% (32/33). Spiral computed tomography performed for long term follow-up revealed occlusion of two vein grafts (3.5 years and 9.7 years) anastomosed to the LAD. CONCLUSIONS: The patency rate of vein grafts anastomosed from prosthetic grafts of the ascending aorta to the native coronary arteries was similar to that of conventional CABG using saphenous vein grafts.

Simplified elephant trunk graft technique for aortic arch replacement.

We refined the elephant trunk graft to facilitate and reinforce the distal anastomosis in aortic replacement operations. A cuff is created in a single four-branch graft, which is used for the distal anastomosis; the trunk below the cuff is inserted into the distal aortic stump. This method is feasible for repairing extensive aortic aneurysm with a fragile wall and for treating acute aortic dissection where thromboocclusion of the remaining false lumen is desired.

Acute myocardial infarction due to left main coronary artery occlusion. Therapeutic strategy.

OBJECTIVE: Acute myocardial infarction due to left main coronary artery occlusion remains catastrophic and mostly fatal due to severe cardiogenic shock and arrhythmia. METHODS: We studied 13 patients undergoing coronary artery bypass grafting for acute myocardial infarction due to left main coronary artery occlusion to clarify the optimal management of these difficult patients. RESULTS: In-hospital mortality was 46.2% (6/13). Revascularization was achieved by catheter intervention followed by bypass surgery in 7, and bypass surgery alone in 6. Two bypass surgery patients without catheter intervention had collateral flow to the left coronary artery, with the right coronary artery dominant. The time from onset to recanalization in the survival group was significantly shorter than in the early death group. CONCLUSIONS: Emergency intervention to preserve left ventricular function or right coronary artery dominant and collateral blood flow to left coronary arteries is important for improving the prognosis of patients with acute myocardial infarction due to left main coronary artery occlusion. If residual left main coronary artery stenosis is significant or other proximal coronary stenosis exists after catheter intervention, early coronary bypass surgery may improve long-term survival.

Successful treatment of a Salmonella aortic arch aneurysm.

A 52-year-old man hospitalized for hoarseness and chest pain was found in chest computed tomography to have an impending aortic arch aneurysm rupture. Laboratory studies showed the presence of severe inflammation. Based on a clinical diagnosis of infected aortic arch aneurysm, we conducted total arch replacement. Salmonella was identified in the aneurismal wall and antibiotics were administered long-term. The postoperative course was uneventful. The patient was discharged on postoperative day 48. He has remained afebrile and asymptomatic in the 10 months since surgery but continues to take 300 mg/d of oral levofloxacin.

Convenient and accurate landing technique for the frozen elephant trunk.

Accurate distal landing is essential to avoid paraplegia while performing the frozen elephant trunk technique (FETT). A 72-year-old man who had a hippocampus-shape aneurysm in the descending aorta was successfully treated by the FETT with a certain and sophisticated method to position the Stent graft precisely using a 16-F nephrostomy balloon catheter. No cerebrospinal complications were observed postoperatively, and computed tomography did not reveal any endleakage.

Aortic root subadventitial hematoma.

A 51-year-old woman was operated on for aortic valve regurgitation 3 months after experiencing chest tightness awakening her from sleep. Intraoperative findings included turbid dark brown pericardial fluid and a nipple-shaped protrusion on the external aspect of the noncoronary sinus of Valsalva. Histologically, the lesion was enclosed by intact media and adventitia, and represented an organized hematoma. Dilated venules noted adjacent to the lesion were suggestive of an intramural hemangioma. The etiology of this lesion is unclear, but it might be an unusual type of intramural hematoma (IMH) and gives us a hint of an origin of IMH.

Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms.

We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca2+ channels expressed separately in mammalian cells. All these Ca2+ channel antagonists blocked T-type Ca2+ channel currents (I(Ca(T))) with distinct blocking manners: I(Ca(T)) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC50s of these Ca2+ channel antagonists to I(Ca(T)) and L-type Ca2+ channel current (I(Ca(L))) were 1.2 micromol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 micromol/l for mibefradil, and 0.35 micromol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca2+ channel.

Remodeling excitation-contraction coupling of hypertrophied ventricular myocytes is dependent on T-type calcium channels expression.

We utilized Wistar rats with monocrotaline (MCT)-induced right ventricular hypertrophy (RVH) in order to evaluate the T-type Ca2+ channel current (ICaT) for myocardial contraction. RT-PCR provides that mRNA for T-type Ca2+ channel alpha1-subunits in hypertrophied myocytes was significantly higher than those in control rats (alpha1G; 264+/-36%, alpha1H; 191+/-34%; P<0.05). By whole-cell patch-clamp study, ICaT was recorded only in hypertrophied myocytes but not in control myocytes. The application of 50 nmol/L nifedipine reduced the twitch tension of the right ventricles equally in the control and RVH rats. On the other hand, 0.5 micromol/L mibefradil, a T-type Ca2+ channel blocker, strongly inhibited the twitch tension of the RVH muscle (control 6.4+/-0.8% vs. RVH 20.0+/-2.3% at 5 Hz; P<0.01). In conclusion, our results indicate the functional expression of T-type Ca2+ channels in the hypertrophied heart and their contribution to the remodeling of excitation-contraction coupling in the cardiac myocyte.

Effect of prostaglandin E1 on ischemia-reperfusion injury during abdominal aortic aneurysm surgery.

OBJECTIVE: Abdominal aortic aneurysm (AAA) surgery subjects the lower extremities to ischemia and reperfusion. Although it is not extensive or prolonged, ischemia of the lower extremities during aortic cross-clamping is gradually and steadily induced. We studied the effects of prostaglandin E1 (PGE1) on ischemia-reperfusion injury of the lower extremities during AAA repair. METHODS: During AAA surgery, two near-infrared spectroscopy probes were positioned on each calf muscle to monitor oxygen metabolism in the lower extremities. We also measured lactate concentration in both iliac veins. RESULTS: Near-infrared spectroscopy signals responded sensitively to aortic cross-clamping and declamping. Lactate increased time-dependently during aortic cross-clamping. The continuous venous administration of PGE1 (20 ng/kg per minute) inhibited the accumulation of lactate during aortic cross-clamping. Declamping of the first iliac artery resulted in a further but transient increase in ipsilateral venous lactate, which may be one component in the mechanism of declamping shock. Prostaglandin E1 eliminated the transient increase in ipsilateral lactate. The administration of PGE1 inhibited the contralateral accumulation of lactate after first declamping, and the lactate level decreased gradually before the second declamping. CONCLUSIONS: Prostaglandin E1 seems to have a protective effect against ischemia-reperfusion injury of the lower extremities during AAA surgery.

Successful surgical treatment of heart failure and ventricular tachycardia in a patient with arrhythmogenic right ventricular dysplasia with cardiomyopathy.

A 70-year-old male patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy demonstrating frequent attacks of ventricular tachycardia (VT) as well as heart failure underwent surgical treatment. Although the patient had severe regurgitation at the mitral and tricuspid valves, the contractility of the right and left ventricles was almost maintained. Annuloplasty of both valves abolished the regurgitation and very effectively controlled heart failure. Surgical cryoablation was performed on the lesion showing the earliest potential before the ORS complex during VT and the arrhythmia was terminated. However, a cardioverter defibrillator was implanted to prevent new VT caused by disease progression.