Early hemodynamics after tibial transverse transport in patients with nonarterial stenosis and arterial stenosis diabetic foot.

BACKGROUND: The diagnosis of peripheral arteriopathy in the diabetic foot is complicated by diabetes and its advanced complications. It has been found that diabetic foot can be categorized into arterial stenosis and non-arterial stenosis, both of which have significant differences in hemodynamic characteristics. AIM: To evaluate the early hemodynamic changes in diabetic foot patients with nonarterial stenosis and arterial stenosis treated by tibial transverse transport (TTT) using high-frequency color Doppler ultrasonography (HFCDU) and a laser Doppler flowmeter. METHODS: Twenty-five patients with Wagner grades 3-5 diabetic foot ulcers were treated with TTT, and the wound healing time and rate were recorded. Patients were grouped according to the results of preoperative lower-extremity ultrasonography. Cases with ≥ 50% stenosis in any of the femoral, popliteal, posterior tibial, anterior tibial, and peroneal arteries of the affected limb were classified as the arterial stenosis group (n = 16); otherwise, they were classified as the nonarterial stenosis group (n = 9). Before and one month after surgery, HFCDU was used to evaluate the degree of lower limb artery lesions and hemodynamic changes in patients. The degree of femoral-popliteal atherosclerotic stenosis, the degree of vascular stenosis and occlusion of the lower-knee outflow tract, and the degree of medial arterial calcification were scored; the three scores were added together to obtain the total score of lower extremity arteriopathy. PeriScanPIM3, a laser Doppler flowmeter system, was used to detect alterations in plantar microcirculation before and 1 mo after surgery. Wound healing and hemodynamic indices were compared between the two groups. RESULTS: The wound healing time of the diabetic foot was significantly shorter in the nonarterial stenosis group than in the arterial stenosis group (47.8 ± 13 vs 85.8 ± 26, P < 0.05), and the wound healing rate of both groups was 100%. The preoperative total lower extremity arteriopathy scores were lower in the nonarterial stenosis group than those in the arterial stenosis group (18.89 ± 8.87 vs 24.63 ± 3.52, P < 0.05). The nonarterial stenosis group showed higher preoperative popliteal artery (POA) blood flow than the arterial stenosis group (204.89 ± 80.76 cc/min vs 76.75 ± 48.49 cc/min, P < 0.05). Compared with the baseline (before surgery), the postoperative POA blood flow of the affected limb in the nonarterial stenosis group decreased one month after surgery (134.11 ± 47.84 cc/min vs 204.89 ± 80.76 cc/min, P < 0.05), while that in the arterial stenosis group increased (98.44 ± 30.73 cc/min vs 61.69 ± 21.70 cc/min, P < 0.05). Although the POA blood flow in the arterial stenosis group was obviously improved one month after surgery, it was still lower than that in the nonarterial stenosis group (98.44 ± 30.73 cc/min vs 134.11 ± 47.84 cc/min, P < 0.05). The nonarterial stenosis group had higher preoperative plantar microcirculation than the arterial stenosis group (56.1 ± 9.2 vs 33.2 ± 7.5, P < 0.05); compared with the baseline, the plantar microcirculation in the arterial stenosis group was significantly improved one month after surgery (51.9 ± 7.2, P < 0.05), while that in the nonarterial stenosis group was reduced (35.9 ± 7.2, P < 0.05). CONCLUSION: Based on preoperative HFCDU findings, diabetic foot patients can be divided into two categories: Those with nonarterial stenosis and those with arterial stenosis, with obvious differences in hemodynamic changes in the early postoperative period between them. In the early stage after TTT, the blood flow volume and velocity and the plantar microcirculation perfusion of the affected limb of the diabetic foot with nonarterial stenosis decreased compared with the baseline, while those of the diabetic foot with arterial stenosis improved significantly compared with the baseline, although both had smoothly healed diabetic foot ulcers.

The implementation of the elastography score in combination with ultrasound prevents unnecessary biopsy of cardiac lesions.

The pathological technique is time consuming, costly, and patients are not preferred routinely. Histopathological findings have very low affectability and greater occurrence of ß-errors, specifically in the diagnosis of cardiomyopathies. Angiography provides a two-dimensional view only. Vascular ultrasound elastography is a comparatively simple diagnostic method with a high resolution of images. The objective of this study was to compare the accuracy of ultrasound, followed by elastography with coronary angiography and endomyocardial biopsy, in the diagnosis of cardiovascular diseases in a Chinese population. A total of 792, patients pathologically abnormal (study group, n=396) and normal (non-study group, n=396), respectively, were included in the experimental diagnostic study. The patients were diagnosed by coronary angiography, endomyocardial biopsy of cardiac lesions, and the Lagrangian speckle model estimator implementation followed by elastography. The study group patients were observed for 38 months after diagnosis. The Mann-Whitney U test followed by Dunnett's multiple comparisons test was used to compare histopathological findings and elastic modulus values between study group and non-study group subjects at a 99% of confidence level. Pathology did reveal a significant cardiac abnormality in the study group patients at baseline. In the angiogram, indistinguishable differences between two distinct parts of the artery were reported. However, the ultrasound images were showed an obvious change in the diameter of the artery for the study group patients (p<0.0001, q=34.301). The histopathological findings were failed to detect a cardiac abnormality in the study group (p=0.0426). However, a significant a cardiac abnormality was observed in elastic modulus values in the study group (p<0.0001 q=4.121). During follow-up, physicians were detected significant cardiovascular diseases in study group patients. Vascular ultrasound elastography is a non-invasive method of diagnostic technique and can increase the confidence of the diagnosis in cases of cardiovascular diseases.

Ultrasound­targeted microbubbles combined with a peptide nucleic acid binding nuclear localization signal mediate transfection of exogenous genes by improving cytoplasmic and nuclear import.

The development of an efficient delivery system is critical for the successful treatment of cardiovascular diseases using non­viral gene therapies. Cytoplasmic and nuclear membrane barriers reduce delivery efficiency by impeding the transfection of foreign genes. Thus, a gene delivery system capable of transporting exogenous genes may improve gene therapy. The present study used a novel strategy involving ultrasound­targeted microbubbles and peptide nucleic acid (PNA)­binding nuclear localization signals (NLS). Ultrasound­targeted microbubble destruction (UTMD) and PNA­binding NLS were used to improve the cytoplasmic and nuclear importation of the plasmid, respectively. Experiments were performed using antibody­targeted microbubbles (AT­MCB) that specifically recognize the SV40T antigen receptor expressed on the membranes of 293T cells, resulting in the localization of ultrasound microbubbles to 293T cell membranes. Furthermore, PNA containing NLS was inserted into the enhanced green fluorescent protein (EGFP)­N3 plasmid DNA (NLS­PNA­DNA), which increased nuclear localization. The nuclear import and gene expression efficiency of the AT­MCB with PNA­binding NLS were compared with AT­MCB alone or a PNA­binding NLS. The effect of the AT­MCB containing PNA­binding NLS on transfection was investigated. The ultrasound and AT­MCB delivery significantly enhanced the cytoplasmic intake of exogenous genes and maintained high cell viability. The nuclear import and gene expression of combined microbubble­ and PNA­transfected cells were significantly greater compared with cells that were transfected with AT­MCB or DNA with only PNA­binding NLS. The quantity of EGFP­N3 plasmids in the nuclei was increased by >5.0­fold compared with control microbubbles (CMCB) and NLS­free plasmids. The gene expression was ~1.7­fold greater compared with NLS­free plasmids and 1.3­fold greater compared with control microbubbles. In conclusion, UTMD combined with AT­MCB and a PNA­binding NLS plasmid significantly improved transfection efficiency by increasing cytoplasmic and nuclear DNA import. This method is a promising strategy for the noninvasive and effective delivery of target genes or drugs for the treatment of cardiovascular diseases.

Comparison of Intracoronary and Intravenous Ultrasound-targeted Microbubble Destruction-mediated Ang1 Gene Transfection on Left Ventricular Remodeling in Canines With Acute Myocardial Infarction.

Intravenous ultrasound-targeted microbubble destruction (IV-UTMD) has made distinct but limited progress in gene therapy. Intracoronary (IC) injection may lead to more gene transfection than IV injection. This study compared the therapeutic effects of IC-UTMD-mediated and conventional IV-UTMD-mediated gene transfection in acute myocardial infarction (MI). A canine MI model was successfully established through transcatheter coronary artery embolism, and the animals were divided into several treatment groups: IC injection with UTMD and the negative control plasmid (IC-UTMD); IC injection of the angiopoietin 1 (Ang1) plasmid (IC-Ang1); IC injection with UTMD and the Ang1 plasmid (IC-UTMD-Ang1); and IV injection with UTMD and the Ang1 plasmid (IV-UTMD-Ang1). At 12 hours after injection, more green fluorescence was observed from the fluorescein isothiocyanate-labeled Ang1 plasmid in the IC-UTMD-Ang1 group. After 1 month, compared with the IV-UTMD-Ang1 group, echocardiography showed that the IC-UTMD-Ang1 group exhibited increased left ventricular systolic function and myocardial infusion, with lower fibrous tissue levels and higher blood vessel density and Ang1 mRNA and protein levels. Similar cardiac troponin I and N-terminal pro-B type natriuretic peptide levels were observed in all groups. Compared with IV-UTMD, IC-UTMD can enhance Ang1 plasmid transfection efficiency after MI, promote gene expression and angiogenesis, and improve left ventricular remodeling without decreasing safety.

Enhanced effect of nuclear localization signal peptide during ultrasound­targeted microbubble destruction­mediated gene transfection.

Ultrasound­targeted microbubble destruction (UTMD) can promote the entry of plasmid DNA (pDNA) into the cell cytoplasm, by increasing the permeability of the cell membrane. But the transfection efficiency remains low due to inability of the pDNA to enter the nucleus. Various methods have been explored to improve the UTMD transfection efficiency, but with little success. In cells, the classic nuclear localization signal (cNLS) peptide is an amino acid sequence that signals proteins that are due for nuclear transport. The present study aimed to investigate whether binding of a cNLS peptide to the pDNA may improve the transfection efficiency of UTMD. Four experimental groups were analyzed: Control group (UTMD + pDNA), group with cNLS (UTMD + pDNA + cNLS), group with mutated NLS (mNLS; UTMD + pDNA + mNLS), and group with cNLS and the nuclear import blocker, wheat germ agglutinin (WGA; UTMD + pDNA + cNLS + WGA). The NLS was labeled by fluorescein isothiocyanate, whereas pDNA was labeled with Cy3. Different molar ratios were tested for the NLS and pDNA combination in order to achieve optimal binding of the two molecules. Human umbilical vein endothelial cells were then transfected using the optimum ultrasonic irradiation parameters and NLS/pDNA molar ratio. At 6 h post­transfection, the rates of Cy3­labeled pDNA inside the cells and their nuclei were detected by flow cytometry and laser confocal microscopy, and the cellular vs. nuclear uptake of pDNA was calculated. In order to further evaluate the effect of NLS on UTMD­mediated gene transfection, the transfection efficiency and relative expression levels of mRNA and protein were detected at 48 h post­transfection. The results demonstrated that the optimal molar ratio of NLS with pDNA was 104:1. The rates of pDNA successful entry into the cell and nucleus were significantly higher in the cNLS group compared with the control group. The transfection efficiency, and relative expression levels of mRNA and protein from the plasmid were significantly increased in the cNLS group compared with the control group. The mNLS group displayed no significant difference compared with the control group, while the WGA group exhibited significant inhibition in most indicators of transfection efficiency compared to the cNLS group. These results suggest that combining a cNLS peptide with pDNA during UTMD­mediated transfection significantly improved transfection efficiency. Thus, a cNLS peptide may be an important mediator and a new strategy in enhancing the efficiency of UTMD­mediated gene transfection.

The differences in left atrial function between ischemic and idiopathic dilated cardiomyopathy patients: A two-dimensional speckle tracking imaging study.

PURPOSE: To evaluate left atrial (LA) function in patients with ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy via two-dimensional speckle-tracking imaging. METHODS: We measured the LA maximum volume, minimum volume, and volume before the atrial systole, and calculated total emptying volume, expansion index, active emptying volume, and fraction. We measured strain and strain rate during systole and late diastole using two-dimensional speckle-tracking imaging, and analyzed correlations between variables. RESULTS: We found no significant differences in LA size, left ventricle (LV) end-diastole diameter, LV ejection fraction (EF), E/A, E/e', deceleration time of the E wave, and effective mitral regurgitant orifice area between the DCM and the ICM group. However, the LA expansion index, active EF, systolic and late diastolic strain, and strain rate were lower in the ICM group (p < 0.05). The expansion index and active EF were positively correlated with the systolic strain rate and the absolute value of the late diastolic strain rate, respectively. CONCLUSIONS: LA basic echocardiographic variables did not reflect the differences between ICM and DCM patients, but the systolic and late diastolic strain, as well as the strain rate, were lower in DCM patients. Two-dimensional speckle-tracking imaging is a promising method to differentiate these patients. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:437-445, 2016.

Renal sympathetic denervation prevents the development of pulmonary arterial hypertension and cardiac dysfunction in dogs.

The renin-angiotensin-aldosterone system is activated in pulmonary arterial hypertension (PAH) patients, and this activation may have long-term negative effects on the progression of PAH. The purpose of this study was to evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the development of pulmonary arterial hypertension and cardiac dysfunction in dogs using two-dimensional speckle tracking imaging. Twenty-two dogs were randomly divided into three groups: control group (n = 7), PAH group (n = 8), and PAH + RSD group (n = 7). All dogs were assessed using two-dimensional speckle tracking imaging. The ventricular strain, ventricular synchrony, left ventricular (LV) twist, and torsion rate were analyzed to evaluate cardiac function. After 8 weeks, the right ventricular lateral longitudinal strain and the septum longitudinal strain were reduced in the PAH group compared with the control group (p < 0.001). However, these values were significantly restored in the PAH + RSD group compared with the PAH group (p < 0.01). The degree of LV and RV dyssynchrony was significantly higher in the PAH group compared with the control group (p < 0.001), but the degree of LV and RV dyssynchrony was significantly lower in the PAH + RSD group compared to the PAH group (p < 0.01). The LV twist was significantly restored in the PAH + RSD group compared to the PAH group (p < 0.01). Similarly, the rotation rate was markedly decreased in the PAH group, and strikingly improved in the PAH + RSD group (p < 0.01). These results indicate that RSD prevents the development of PAH and cardiac dysfunction in dogs.

Renal sympathetic denervation inhibits the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs.

BACKGROUND: The purpose of this study was to investigate whether transcatheter renal sympathetic denervation (RSD) interfere with the development of left ventricular (LV) mechanical dyssynchrony during the progression of heart failure (HF). METHODS: Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (seven dogs), and RSD group (six dogs). Sham-operated group were implanted with pacemakers without pacing; Control group were implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Both LV strain and LV dyssynchrony were analyzed via 2D speckle-tracking strain echocardiography to evaluate LV function. Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain on apical 4- and 2-chamber views. Radial and circumferential dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in mid- and base-LV short-axis views. Each myocardial function was also evaluated by averaging the peak systolic strains. LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) were measured. The LV interstitial fibrosis was determined by histological analysis. Plasma angiotensin II (Ang II), aldosterone and norepinephrine (NE) levels were also measured. RESULTS: After 3 weeks, all of the dogs in both the control and RSD groups showed greater LV end-diastolic volume compared with the sham-operated group; however, the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the control group (p<0.001). The LV systolic strains were higher in the RSD group than in the control group (p<0.001 for longitudinal, circumferential and radial strain, respectively). The levels of LV dyssynchrony were lower in the RSD group than in the control group (p<0.001 for longitudinal, circumferential and radial dyssynchrony, respectively). Compared with dogs with control alone, RSD dogs had lower LV end-diastolic pressures and less fibrous tissue. The levels of plasma Ang II, aldosterone and NE were lower in the RSD group than in the control group. CONCLUSIONS: RSD inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs.

Alteration in the global and regional myocardial strain patterns in patients with inferior ST-elevation myocardial infarction prior to and after percutaneous coronary intervention.

This study was designed to investigate the alteration on regional and global strains of left and right ventricle (LV, RV) in patients with inferior wall ST-elevation myocardial infarction (MI). Patients were examined prior to and 7 days after percutaneous coronary intervention (PCI) using speckle-tracking techniques. Fifty-nine patients (36 males and 23 females) and 60 healthy controls (40 males and 20 females) were enrolled in this study. LV strains were measured from three deformations including radial, longitudinal, and circumferential. RV strains were measured only from the longitudinal. Three types of LV global strains were significantly lower in patients than in controls, and LV global longitudinal and circumferential strains were moderately improved by PCI. The LV regional strains reduced significantly in most of the segments (87%) after inferior wall MI and over half of them (60%) were improved by PCI. The RV global longitudinal strains were significantly lower in patients than in controls, and they were moderately improved by PCI. In conclusion, the regional and global strains of LV and RV were reduced in patients with inferior wall MI, and PCI most markedly improved the global strains and regional strains of the infarct and adjacent myocardium in the apical and middle levels.

Ultrasound microbubbles combined with the NFκB binding motif increase transfection efficiency by enhancing the cytoplasmic and nuclear import of plasmid DNA.

Inefficient gene delivery poses a challenge for non­viral gene therapy. Cytoplasmic and nuclear membrane barriers are responsible for the inefficiency as they restrict the import of exogenous genes. The present study aimed to improve the transfection efficiency using a novel gene delivery system, which consisted of two components: ultrasound microbubbles and the nuclear factor κB (NFκB) binding motif. Ultrasound-targeted microbubble destruction (UTMD) was used to enhance the cytoplasmic import of plasmids and the NFκB binding motif was added to promote the nuclear intake of the plasmid from the cytoplasm. In the present study, human umbilical vein endothelial cells were transfected using UTMD with two different Cy3-labeled plasmids, phSDF-1α and phSDF­1α­NFκB. phSDF-1α-NFκB was constructed by inserting a specific DNA targeting sequence (five optimal repeats of the binding motif for the inducible transcription factor NFκB) into phSDF­1α. The nuclear import and gene expression efficiency of phSDF-1α-NFκB were compared with those of phSDF-1α to investigate the effect of the NFκB binding motif on transfection. The results showed that UTMD significantly increased the cytoplasmic intake of pDNA and maintained high cell viability. The nuclear import and gene expression of phSDF-1α­NFκB­transfected cells were significantly higher than those transfected with phSDF-1α. Compared with the NFκB­free plasmids, the quantity of NFκB plasmids in the nucleus increased 6.5-fold and the expression of SDF-1α was 4.4-fold greater. These results suggest that UTMD combined with NFκB binding motif significantly improve transfection efficiency by enhancing the cytoplasmic and nuclear import of exogenous plasmid DNA.

Evaluation of left ventricular mechanical dyssynchrony in chronic heart failure patients by two-dimensional speckle tracking imaging.

The purpose of this study was to evaluate left ventricular mechanical dyssynchrony (LVMD) in chronic heart failure (CHF) patients using two-dimensional speckle tracking imaging (2D-STI), and also to compare the usefulness of three patterns of myocardial deformation in mechanical dyssynchrony assessment. Furthermore, the relationships between left ventricular ejection fraction (LVEF), QRS duration (QRSd), and LVMD were explored. In total, 78 patients and 60 healthy individuals (group 3) were enrolled. The patients were classified into two subgroups: LVEF≤35% (group 1), 35%0.05). CHF patients have different extents of LVMD. Longitudinal deformation shows the best detectability of dyssynchrony motion. Left ventricular systolic function was closely related to mechanical dyssynchrony, whereas QRSd showed no significant correlation.

Optimization of transfection parameters for ultrasound/SonoVue microbubble-mediated hAng-1 gene delivery in vitro.

This study aimed to explore the effects of microbubble concentration, gene dosage, cell-microbubble mixing mode and fetal bovine serum (FBS) on gene delivery. 293T cells were transfected with Sonovue microbubbles carrying the hAng-1 gene via ultrasound irradiation. Various ultrasound exposure parameters and microbubble and DNA concentrations were investigated. In addition, FBS and the cell suspension or adherent mode was explored. Transfection efficiency and cell viability were used to determine the optimal transfection parameters. hAng-1 gene transfection efficiency gradually increased with elongation of ultrasound exposure and increasing microbubble concentration. However, if ultrasound irradiation exceeded 1.5 W/cm² and 30 sec or the microbubble concentration was over 20%, hAng-1 gene expression was significantly decreased, coupled with extensive cell death. Gene transfection levels were low under DNA concentrations less than 15 µg/ml. Furthermore, the gene transfer rate was significantly increased under cell suspension mode; FBS had no effect on hAng-1 gene transfection. The integrity of hAng-1 DNA was not affected by ultrasonic irradiation under optimal conditions. The optimal transfection parameters for the hAng-1 gene and Sonovue microbubble were ultrasound exposure of 1.5 W/cm² and 30 sec, 20% microbubbles, 15 µg/ml of DNA and under cell suspension mode.

Evaluation of left ventricular mechanical dyssynchrony in patients with heart failure after myocardial infarction by real-time three-dimensional echocardiography.

OBJECTIVE: To evaluate the incidence and prevalence of left ventricular (LV) dyssynchrony in patients with heart failure after myocardial infarction (MI) by real- time three-dimensional echocardiography (RT-3DE), and to investigate the clinical application value of using RT-3DE as a method of providing more detailed information for clinical strategy. METHODS: This cross-sectional study was carried out in Renmin Hospital of WuHan University, Hubei Province, China from July 2009 to December 2010. The RT-3DE was performed on 43 patients with chronic heart failure after MI and 30 normal subjects, to analyze LV volume and left ventricular ejection fraction (LVEF), also the LV systolic dyssynchrony index (SDI). RESULTS: The dyssynchrony rate of the total MI patients was 83.7%, and was 100% in the severe dysfunction group. The SDI of MI patients was significantly higher than the control subjects (p less than 0.01), and the SDI of those whose LVEF

Misdiagnosis of aorta-right atrial tunnel.

First reported by Coto in 1980, aorta-right atrial tunnel (ARAT) is a rare congenital vascular connection between the aortic root and RA. The case report presents a 38-year-old male patient with ARAT. Echocardiography showed a tunnel-like structure which appeared to be a connection between the left coronary sinus and the left atrium although the tunnel was connected to the right atrium. The misdiagnosis may be explained that the images were overlaid and abnormal color flow signal was not detected in RA because of the failure to detect color flow spectrum at the outlet of superior vena cava (SVC). We have discussed the diagnostic experience of the rare congenital cardiac anomaly in echocardiography: (1) carefully detect the origin and termination of abnormal tunnel structure; (2) the outlet of SVC into RA should be detected for possible artery flow spectrum and color flow signal into RA; (3) transesophageal echocardiography should be performed for identifying the diagnosis of ARAT if it is necessary.

[Application of high frequency ultrasound to the diagnosis of varicocele in infertile males].

OBJECTIVE: To investigate the objective index of the diagnosis of varicocele (VC) in infertile males by ultrasonography and the testis volume changes resulting from varicocele. METHODS: Forty-six healthy male volunteers and 178 infertile men with left varicocele were detected by high frequency ultrasound. According to the clinical data and ultrasonographic results, the 178 VC patients were divided into 4 groups, SVC group (45 cases), VC I group (44 cases), VC II group (48 cases), and VC III group (41 cases). RESULTS: (1) The differences in DR, DV, Vmax, TR and testis volume between the right and the left sides were not statistically significant in the control group (P > 0.05). (2) The differences in DR, DV, Vmax and TR between the experimental and control groups as well as among the VC groups were statistically significant (P < 0.001). (3) The left testis volume was smaller than the right among the VC groups (P < 0.01). The right testis volume of the VC II and VC III groups was significantly smaller than that of the control group ( P < 0.05), and the left testis volume in the VC III group was significantly smaller than that of the SVC group (P < 0.05). CONCLUSION: (1) High frequency ultrasound can detect the accurate diameter of the internal spermatic vein, hemodynamic index and testis volume of infertile men with VC, and hence help to screen the causes of male infertility. (2) Unilateral varicocele can cause a volume decrease in both testes, especially in the left. Both unilateral SVC and VC can cause testicular atrophy, and the more serious VC, the higher testicular atrophy.