Masahiro Kohzuki

Relationship Between Fluoroscopic Time, Dose–Area Product, Body Weight, and Maximum Radiation Skin Dose in Cardiac Interventional Procedures

OBJECTIVE Real-time maximum dose monitoring of the skin is unavailable on many of the X-ray machines that are used for cardiac intervention procedures. Therefore, some reports have recommended that physicians record the fluoroscopic time for patients undergoing fluoroscopically guided intervention procedures. However, the relationship between the fluoroscopic time and the maximum radiation skin dose is not clear. This article describes the correlation between the maximum radiation skin dose and fluoroscopic time for patients undergoing cardiac intervention procedures. In addition, we examined whether the correlations between maximum radiation skin dose and body weight, fluoroscopic time, and dose-area product (DAP) were useful for estimating the maximum skin dose during cardiac intervention procedures. MATERIALS AND METHODS Two hundred consecutive cardiac intervention procedures were studied: 172 percutaneous coronary interventions and 28 cardiac radiofrequency catheter ablation (RFCA) procedures. The patient skin dose and DAP were measured using Caregraph with skin-dose-mapping software. RESULTS For the RFCA procedures, we found a good correlation between the maximum radiation skin dose and fluoroscopic time (r = 0.801, p < 0.0001), whereas we found a poor correlation between the maximum radiation skin dose and fluoroscopic time for the percutaneous coronary intervention procedures (r = 0.628, p < 0.0001). There was a strong correlation between the maximum radiation skin dose and DAP in RFCA procedures (r = 0.942, p < 0.0001). There was also a significant correlation between the maximum radiation skin dose and DAP (r = 0.724, p < 0.0001) and weight-fluoroscopic time product (WFP) (r = 0.709, p < 0.0001) in percutaneous coronary intervention procedures. CONCLUSION The correlation between the maximum radiation skin dose with DAP is more striking than that with fluoroscopic time in both RFCA and percutaneous coronary intervention procedures. We recommend that physicians record the DAP when it can be monitored and that physicians record the fluoroscopic time when DAP cannot be monitored for estimating the maximum patient skin dose in RFCA procedures. For estimating the maximum patient skin dose in percutaneous coronary intervention procedures, we also recommend that physicians record DAP when it can be monitored and that physicians record WFP when DAP cannot be monitored.

Endothelin-1 augments pressor response to angiotensin II infusion in rats.

To assess possible roles of endothelin in the regulation of blood pressure, we studied effects of a subpressor dose of endothelin-1 (3 micrograms/kg/day) on chronic blood pressure responses to infusion of angiotensin II and norepinephrine in rats. Rats were infused with angiotensin II at a subpressor dose (400 micrograms/kg/day i.p.) or with norepinephrine at a subpressor dose (360 micrograms/kg/day i.p.) for 6 days. Systolic blood pressure was significantly elevated during combined infusion of endothelin-1 and angiotensin II, whereas endothelin-1 alone or angiotensin II alone failed to induce any significant changes in systolic blood pressure compared with vehicle alone. This effect was sustained for the whole experimental period and was not associated with any significant changes in body weight, fluid intake, urine volume, or urinary electrolyte excretion. In contrast, combined infusion of endothelin-1 and norepinephrine failed to elevate systolic blood pressure, and no significant difference in systolic blood pressure was observed for the whole experimental period among the four groups of rats with endothelin-1 in combination with norepinephrine, endothelin-1 alone, norepinephrine alone, and vehicle alone. The present results indicate that angiotensin II and endothelin-1, but not norepinephrine and endothelin-1, work synergistically to raise the blood pressure and also suggest the possibility that endothelin-1 may modulate blood pressure control.

Antihypertensive and renal-protective effects of losartan in streptozotocin diabetic rats.

Objective To assess the renal benefits of a specific angiotensin II receptor antagonist, losartan, in diabetic rats with renal impairment. Design and methods Uninephrectomized streptozotocin diabetic spontaneously hypertensive rats (SHR) were randomly assigned to receive vehicle, or to receive losartan or captopril, or both, intraperitoneally via osmotic minipumps for 8 weeks. Results Blood pressure and urinary protein excretion in the diabetic SHR increased progressively during the experimental period. Both captopril treatment and losartan treatment completely blocked the development of hypertension in diabetic SHR. Simultaneous administration of captopril and losartan did not enhance the antihypertensive effects of losartan treatment or captopril treatment. Furthermore, losartan treatment, captopril treatment and losartan + captopril treatment all significantly decreased urinary protein excretion, urinary albumin excretion and serum creatinine to the same extent. These effects were sustained for the entire experimental period and were not associated with any significant changes in body weight, urine volume, urine sugar and urinary electrolytes excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. Losartan treatment, captopril treatment and losartan + captopril treatment all significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. Losartan treatment and captopril treatment both significantly attenuated the increase in heart weight: body weight ratio. The heart weight: body weight ratio in the losartan-treated group was significantly lower than in the captopril-treated group. Conclusions These results indicate that hypertension could accelerate diabetic renal impairment and that losartan has antihypertensive and renoprotective effects in this rat model. They also suggest that the antihypertensive and renoprotective effects of captopril treatment in this rat model are caused mainly by inhibition of angiotensin II production rather than stimulation of the kallikrein-kinin system or of vasodilator prostaglandins. The difference in potency between losartan treatment and captopril treatment to attenuate the increase in heart weight: body weight ratio might partly explain the existence in the heart of angiotensin-forming pathways, which are not dependent on angiotensin converting enzyme.

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure

Objectives Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. Design and methods Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. Results Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1–4) remained in the model as a significant predictors of mean proteinuria (weeks 1–4) (all P < 0.0001). Conclusions These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

Radiation Dose of Interventional Radiology System Using a Flat-Panel Detector

OBJECTIVE Currently, cardiac interventional radiology equipment has tended toward using flat-panel detectors (FPDs) instead of image intensifiers (IIs) because FPDs offer better imaging performance. However, the radiation dose from an FPD in cardiac interventional radiology is not clear. The purpose of our study was to measure the radiation doses during cineangiography and fluoroscopy of many cardiac radiology systems that use FPDs or IIs, in clinical settings. MATERIALS AND METHODS This study examined 20 radiology systems in 15 cardiac catheterization laboratories (11 used FPD and nine used II). The entrance surface doses with digital cineangiography and fluoroscopy were compared for the 20 systems using acrylic plates (20-cm thick) and a skin dose monitor. RESULTS For fluoroscopy, the average entrance surface doses of the 20-cm-thick acrylic plates were identical for FPD (average +/- SD, 16.63 +/- 7.89 mGy/min; range, 5.7-26.4 mGy/min; maximum/minimum, 4.63) and II (17.81 +/- 12.52 mGy/min; range, 6.5-42.2 mGy/min; maximum/minimum, 6.49) (p = 0.799). For digital cineangiography, the average entrance surface dose of the 20-cm-thick acrylic plate was slightly lower with FPD (29.68 +/- 16.40 mGy/10 s; range, 8.9-58.5 mGy/10 s; maximum/minimum, 6.57) than with II (38.50 +/- 33.71 mGy/10 s; range, 15.2-117.1 mGy/10 s; maximum/minimum, 7.70), although the difference was not significant (p = 0.487). CONCLUSION We found that the average entrance doses of cineangiography and fluoroscopy in FPD systems were not significantly different from those in II systems. Hence, FPDs did not inherently reduce the radiation dose, although FPDs possess good detective quantum efficiency. Therefore, to reduce the radiation dose of cardiac interventional radiology systems, even FPD systems, practical measures are necessary.

Gene expression of (pro)renin receptor is upregulated in hearts and kidneys of rats with congestive heart failure

Recent studies have revealed that (pro)renin receptor ((P)RR), a newly identified member of the renin-angiotensin system, was associated with organ damage in the kidney. However, there has been little information for (P)RR in hearts. To investigate the regulation of (P)RR in heart failure, we examined the expression of (P)RR in hearts and kidneys of rats with congestive heart failure (CHF) due to coronary ligation by quantitative RT-PCR and immunohistochemistry. Significantly increased levels of (P)RR mRNA were found in the atrium, right ventricle, non-infarcted part of left ventricle, infarcted part of left ventricle and kidney of CHF rats, when compared with sham operated rats (about 1.6-fold, 1.4-fold, 1.6-fold, 1.7-fold and 1.5-fold, respectively). Expression levels of mRNAs encoding renin and angiotensinogen in these heart and kidney tissues were also increased in the CHF rats. Immunohistochemistry showed positive (P)RR immunostaining in the myocardium, the renal tubular cells, and vascular smooth muscle and endothelial cells in the heart and the kidney. The renal tubular cells were more intensely immunostained in CHF rats than in sham operated rats. These findings suggest that the expression of (P)RR is increased in the hearts and kidneys of rats with heart failure, and that (P)RR may contribute to heart failure.

Measurement of angiotensin converting enzyme induction and inhibition using quantitative in vitro autoradiography : tissue selective induction after chronic lisinopril treatment

Angiotensin converting enzyme (ACE) inhibitors lead to induction of ACE in animals and humans. This complicates the use of ACE enzymatic activity as an index of inhibition in plasma or tissues after chronic administration of ACE inhibitors. We have, therefore, developed a method for ACE measurement by in vitro autoradiography using an 125I-labelled inhibitor to quantitate total ACE and the concentration of free (not inhibited) ACE in tissues after prolonged administration of ACE inhibitors to rats. Measurements made on unprocessed tissue sections reflect residual free ACE activity in the presence of the unlabelled inhibitor. In a parallel series of adjacent sections, the ACE inhibitor is dissociated from the enzyme by reversibly denaturing the enzyme by zinc chelation. This is followed by reconstitution of the active enzyme by zinc ion replacement and measuring total enzyme concentration. This technique permits measurement of the extent of ACE inhibition and induction. This method was evaluated in tissues of rats following chronic oral administration of lisinopril (10 mg/kg per day) for 2 weeks. The pattern of ACE inhibition was similar to that seen in our previous acute studies. However, induction of ACE was found to be organ specific; plasma total ACE increased 1.75-fold and total ACE in the lung increased by 30% compared with untreated animals, but there was no demonstrable change in total ACE concentration in the kidney, adrenal or aorta. Despite this, during chronic treatment with lisinopril, ACE activity in all of these organs was inhibited with low levels of free ACE.(ABSTRACT TRUNCATED AT 250 WORDS)

Total Entrance Skin Dose: An Effective Indicator of Maximum Radiation Dose to the Skin During Percutaneous Coronary Intervention

OBJECTIVE A number of cases of radiation-associated patient skin injury during percutaneous coronary intervention (PCI) have been reported. To protect against this complication, maximum skin dose to the patient should be monitored in real time. Unfortunately, in most cardiac intervention procedures, real-time monitoring of maximum skin dose is not possible. Angiographic X-ray units, however, display the patients total entrance skin dose in real time. We therefore investigated the relation between maximum skin dose and total entrance skin dose to determine whether total entrance skin dose can be used to estimate maximum skin dose during PCI. MATERIALS AND METHODS The dose-area product was measured, and maximum skin dose and total entrance skin dose were calculated with a skin-dose-mapping software program. The target vessels of 194 PCI procedures were divided into four groups according to the American Heart Association (AHA) segment system. RESULTS The maximum skin dose constituted 48%, 52%, 50%, and 52% of the total entrance skin dose during PCI on AHA segments 1-3, 4, 5-10, and 11-15, respectively. There were significant correlations between maximum skin dose and total entrance skin dose during PCI (r = 0.894, 0.935, 0.859, and 0.898 for segments 1-3, 4, 5-10, and 11-15, respectively; p < 0.001). CONCLUSION Maximum skin dose during PCI is approximately 50% of the total entrance skin dose for each target vessel. Correlation between the two doses was very good. Total entrance skin dose is an effective predictor of maximum skin dose during PCI when the formula used is maximum skin dose = 0.5 x total entrance skin dose. Our results provide useful information for avoiding deterministic radiation skin injury to patients undergoing PCI.

Effect of Aging on Cough and Swallowing Reflexes: Implications for Preventing Aspiration Pneumonia

The impairment of airway protective reflexes, i.e., swallowing and cough reflexes, is thought to be one of the major causes for aspiration pneumonia in older people. Restoration of cough and swallowing reflexes in the elderly is key to preventing aspiration pneumonia in the elderly. Although, the medical literature has asserted that cough and swallowing are controlled primarily by the brainstem, recent advances in human brain imaging has provided evidence that cortical and subcortical structures play critical roles in cough and swallowing control. Because of their nature, reflexive cough and swallowing activate both sensory and motor areas in the cortex. In both protective reflexes, the sensory component, including sensory cortex in reflexive circuits, seems to be more vulnerable to aging than the motor component, including the motor cortex. Therefore, the strategy to restore cough and swallowing reflexes should be focused on compensations of sensory components in these reflexive circuits. Remedies to enhance sensory nerve terminals and sensory cortical areas related to these reflexes might be useful to prevent aspiration pneumonia in the elderly.

Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle.

1 Low‐voltage electrical stimulation (LVES) in skeletal muscle at a level far below the threshold of muscle contraction has been reported to promote local angiogenesis. However, the mechanism underlying the promotion of local angiogenesis by LVES has not been fully elucidated. In the present study, we evaluated whether angiogenic factors, such as vascular endotherial growth factor (VEGF), hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), as well as other disadvantageous factors, such as inflammation (interleukin (IL)‐6) and hypoxia (hypoxia‐inducible factor (HIF)‐1α), contribute to the local angiogenesis produced by LVES. 2 We completely excised bilateral femoral arteries of male Sprague‐Dawley rats. After the operation, electrodes were implanted onto the centre of the fascia of the bilateral tibialis anterior (TA) muscles, tunnelled subcutaneously and exteriorized at the level of the scapulae. The right TA muscles of rats were stimulated continuously at a stimulus frequency of 50 Hz, with a 0.1 V stimulus strength and no interval, for 5 days. The left TA muscles served as controls. 3 We found that both VEGF and HGF protein were significantly increased by LVES in stimulated muscles compared with control. The VEGF level of the LVES group was 89.10 ± 17.19 ng/g, whereas that of the control group was 65.07 ± 12.88 ng/g, as determined by ELISA (P < 0.05). The HGF level of the LVES and control groups was 8.52 ± 1.96 and 5.80 ± 2.14 ng/g, respectively (P < 0.05). In contrast, there was no difference in FGF, IL‐6 and HIF‐1α between the LVES and control groups. 4 These results suggest that LVES in a hindlimb ischaemia model of rats increases not only VEGF, but also HGF, production, which may be the main mechanism responsible for the angiogenesis produced by LVES.